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Hyaluronic Acid: Not with cancer, never with aromatase inhibitors.

 

Subject: Hyaluronic Acid, although promoted for many therapeutic uses, including counteracting side effects of aromatase inhibitors, may promote growth and spread of cancer cells and should not be used by cancer patients.

 

Please Note:  Not everyone agrees with the opinion I express in this newsletter.  Bill Sardi, the author of a book on hyaluronic acid sent me a dissenting opinion which you can read at this [link]

 

Life is rarely as simple as we would like. In nutritional medicine as in many other fields, we naively expect things to be clear cut, black and white, good or bad. We want a nutritional supplement to be good for you; good in any amount, for anybody, at any time and in any form. If you can nominate anything to fulfill that description please let me know. These ramblings are brought up by the reading I've been doing on Hyaluronic acid.

 

Hyaluronic acid is also known as hyaluronen (typing either term is tedious so I will abbreviate it as HA for the rest of this letter) is a relatively new on the market and is being promoted for a vast range of therapeutic uses. I am not going to focus on potential beneficial uses; this is a cautionary letter. This chemical appears important in the growth and spread of cancer tumors and should be avoided by anyone with cancer, particularly patients with breast cancer.

 

Patients have told me that HA relieves some of the side effects caused by aromatase inhibitors. Even if it does, they should still not take HA.

 

Hyaluronic acid (HA) was first used commercially in 1942 when Endre Balazs applied for a patent to use it as a substitute for egg white in bakery products. HA is found throughout the human body, in the synovial fluid, extracellular membrane, connectitive tissues, eyes etc. In simple terms it provides structure to the body: kind of like the jello goop that holds us together. It moistens, lubricates and fills in the empty spaces in our bodies Websites selling HA make a range of claims and suggest using it to treat: fractures, hernias, glaucoma, keratoconus, detached retinas, osteoarthritis, muscle contractures, TMJ, scarring, vocal cord insufficiency, wrinkled skin, cartilage damage, wound healing and ligament healing

 

Not everyone agrees that HA will really work for these conditions. Medically oriented websites, not in the business of selling HA supplements, point out that HA is not absorbed when taken orally and that oral supplements should have no effect. While decrying the oral use of HA, they often promote use by injection at their hospital. Yet even the injected HA used to treat osteoarthritis has produced mixed results.

 

HA probably does have some effect when taken orally; patients tell me that it relieves some of the joint discomfort they experience as a side effect while taking aromatase inhibitors.[more info on aromatase inhibitors] These drugs, Arimidex is the most widely used, block estrogen production completely. They are the new drug of choice to prevent breast cancer recurrence, probably soon to supplant tamoxifen. The research on aromatase inhibitors looks good (so far) and they may be safer and more effective than tamoxifen. Unfortunately the aromatase inhibitors may cause some uncomfortable side effects. Stopping estrogen production as dramatically as they do, tends to “dry up” the body. Tissue becomes less moist, wrinkles become more obvious and most importantly, joints tend to feel irritated, sore and inflamed.

 

Thus HA would seem to be an obvious solution to these unwanted side effects. Several of my patients who experience relief taking HA have not been happy when I tell them to stop taking it.

 

We don't want any extra HA to be anywhere near cancer cells. It appears to make it easier for cancer to spread. When a cancer tumor wants to expand its size and spread into adjacent territory, the cells have to move out into the extra cellular matrix. They do this by forming an arm of cytoplasm that reaches out, grabs onto a handhold in adjacent goop and than pulls the cell along after it. How does it latch onto this goop? Imagine it's got a chunk of Velcro at the tip of the arm. In this analogy the Velcro is designed to latch onto a specific chemical which turns out to be hyaluronic acid. The ‘Velcro' has been identified and named; it is a specific protein made by many cancer cells named CD44.

 

When a cancer cell with this CD44 protein grows and attempts to spread, HA helps it do so. [i] If you add extra HA to a culture of CD44 positive breast cancer cells they grow and spread faster. [ii] [iii] Another study demonstrates HA increases attachment of breast and ovarian cancer. [iv] In mice with breast cancer, if you add hyaluronidase, the enzyme that digests and breaks up HA, you slow the growth and progression of the cancer. This enzyme works so well at hindering cancer spread that research is being conducted using it as a treatment for cancer. [v] An older study shows that this enzyme, hyaluronidase, enhances the anticancer activity of the chemotherapy drug adryamicin. [vi]

 

The research isn't all bad though. One study in which HA was injected directly into tumors suggests it hinders tumor cell attachments [vii] . This situation may be similar to how modified citrus pectin inhibits metastasis. The vast amount of free floating unattached HA from the injection may coat the CD44 binding sites preventing the cell from latching onto the HA in the extracellular matrix. Kind of like what happens when you wash Velcro with a wool sweater, the Velcro becomes useless. This is just speculation on my part. The majority of research argues against HA. Orally taken HA will never reach the tissue concentrations used in this experiment.

 

One study demonstrates HA increases attachment of breast and ovarian cancer. [viii] Cancer cells seem to want to degrade, or simply put, eat, hyaluronen. The more capable they are at degrading HA, the more invasive they are. [ix] This HA business is also important in other cancers as well including, lung cancer [x] , ovarian cancer [xi] . When the CD44 velcro protein latches onto a healthy cell, it stimulates the cell to make more HA and the cancer cells somehow use the extra HA for their own benefit. [xii]

 

This knowledge about HA and cancer is well enough understood that researchers are using it to devise new cancer treatments. They make oligomers, chemicals that look very similar to HA, and use these almost look-a-like chemicals to block tumor growth. [xiii]

 

Obviously given this background, Hyaluronic acid should not be taken by anyone with breast cancer, ovarian cancer or lung cancer. By extension, although at this point unproven, it should not be taken by people with other cancers either.

 

We often mistakenly think that natural things are inherently safer than drugs. This could be certainly assumed if we are considering a natural substance in its natural form and which has a long history of use either as a medicine or as a food. Natural substances which do not have this history of use may just as likely be poisonous. When we isolate components of natural substances, and concentrate them, we are making drugs. As much as we may complain about the shenanigans of pharmaceutical companies ignoring research indicating the danger of their products, at least they are doing the research. We have entered an era in which “natural substances” are refined to the degree that we should consider them pharmaceuticals and be wary in randomly prescribing them untested.

 

[i] Int J Cancer. 1999 Jul 2;82(1):77-83.   

Human breast-cancer metastasis formation in a nude-mouse model: studies of hyaluronidase, hyaluronan and hyaluronan-binding sites in metastatic cells.

 

Victor R, Chauzy C, Girard N, Gioanni J, d'Anjou J, Stora De Novion H, Delpech B.

 

Laboratoire d'Oncologie Moleculaire, Centre Henri-Becquerel, Rouen , France.

Few animal models are available to study metastasis formation. The purpose of the present study was to obtain a useful model of metastasis formation in nude mice in an attempt to analyze the stroma reaction and in particular the production and the expression of hyaluronan (HA), hyaluronidase, and HA-binding sites by cultivated cells, and HA and hyaluronectin (HN) in the invasive areas of tumors. Nude mice were subjected to i.p. injections of several human cancer cell lines (PLC/PRF/5, HepG2, CB 191, CB 193, PC3, CAL 51, SA 87 and SA 98), and formation of metastases was analyzed in different organs (lung, liver, kidney, spleen and axillary nodes) by immunohistochemical techniques. CAL 51, a breast-cancer-metastasis-derived cell line with a normal karyotype, produced i.p. tumors in 75% animals and metastases in 90% animals (detected in the liver and axillary nodes). Two modes of invasion by CAL 51 cells were observed in the liver: one, direct, from the surface of the liver and the other, indirect, via the bloodstream. HA and HN were strongly expressed at the invasion areas. A cell line derived from hepatic metastasis of CAL 51 (HMD CAL 51) presented an abnormal karyotype. HMD CAL 51 produced more hyaluronidase (12-fold) and HA (10-fold) and expressed more CD44 (1.6-fold) and other HA-binding sites (9.5-fold) than the established cell line CAL 51. Our results show that i.p. injection of the CAL 51 cell line into nude mice provides a useful model of metastasis formation. The passage of the CAL 51 cells from the primary state to the metastatic state was characterized by a dramatic increase of HA and hyaluronidase production, and expression of HA, HN and HA-binding sites.

 

PMID: 10360824 [PubMed - indexed for MEDLINE]

 

[ii] Int J Exp Pathol. 2001 Jun;82(3):193-200.

Effects of hyaluronan on the invasive properties of human breast cancer cells in vitro.

Herrera-Gayol A, Jothy S.

 

Department of Pathology, McGill University , Montreal , Quebec , Canada .

 

Hyaluronan (HA) is a high molecular weight glycosaminoglycan present mostly in the extracellular matrix (ECM). HA binds to specific receptors such as CD44. Its production is increased at the tumour-stroma interface, including those in breast cancer tumours. It has been suggested that it facilitates invasion of tumour cells into the ECM by a hydrodynamic effect, or by altering tumour cell behaviour. Using in vitro tests we studied the effect of immobilized (iHA) and soluble (sHA) HA on the invasive properties of four human breast cancer cell lines with different levels of CD44 expression. Our results show that iHA acts as an adhesive, haptotactic, and motility stimulating factor for the CD44 positive Hs578T cells and induces the expression of membrane CD44. sHA also changes the motility properties of the Hs578T and MDA-231 cells and increases their CD44 expression. sHA or iHA have no measurable effect on the adhesion, motility or CD44 expression of the ZR-75-1 and MCF-7 breast cancer cells. Our results establish that in high CD44 expressing breast cancer cells HA modulates tumour cell adhesion and motility and also increases the expression of its own receptor, CD44.

 

PMID: 11488992 [PubMed - indexed for MEDLINE]

 

[iii] Int J Exp Pathol. 2001 Jun;82(3):193-200.

Effects of hyaluronan on the invasive properties of human breast cancer cells in vitro.

Herrera-Gayol A, Jothy S.

 

Department of Pathology, McGill University , Montreal , Quebec , Canada .

 

Hyaluronan (HA) is a high molecular weight glycosaminoglycan present mostly in the extracellular matrix (ECM). HA binds to specific receptors such as CD44. Its production is increased at the tumour-stroma interface, including those in breast cancer tumours. It has been suggested that it facilitates invasion of tumour cells into the ECM by a hydrodynamic effect, or by altering tumour cell behaviour. Using in vitro tests we studied the effect of immobilized (iHA) and soluble (sHA) HA on the invasive properties of four human breast cancer cell lines with different levels of CD44 expression. Our results show that iHA acts as an adhesive, haptotactic, and motility stimulating factor for the CD44 positive Hs578T cells and induces the expression of membrane CD44. sHA also changes the motility properties of the Hs578T and MDA-231 cells and increases their CD44 expression. sHA or iHA have no measurable effect on the adhesion, motility or CD44 expression of the ZR-75-1 and MCF-7 breast cancer cells. Our results establish that in high CD44 expressing breast cancer cells HA modulates tumour cell adhesion and motility and also increases the expression of its own receptor, CD44.

 

PMID: 11488992 [PubMed - indexed for MEDLINE]

 

[iv] Am J Pathol. 1996 Jun;148(6):1733-40.

Increased hyaluronan at sites of attachment to mesentery by CD44-positive mouse ovarian and breast tumor cells.

Yeo TK, Nagy JA, Yeo KT, Dvorak HF, Toole BP.

 

Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston , MA 02111 , USA .

 

The mouse ovarian ascites tumor, MOT, and mammary ascites tumor, TA3/St, served as models to follow changes in hyaluronan levels during tumor growth, attachment, and invasion. Subsequent to introduction of tumor cells into the peritoneal cavity, hyaluronan accumulated intraperitoneally and at the initial sites of attachment of tumor cells and cell clumps to the mesenteric surface; the latter co-localized with sites of fibrin deposition as reported earlier. Subsequently, high levels of hyaluronan accumulated throughout the interior of the mesentery. Because neither tumor cell line synthesized substantial amounts of hyaluronan in culture, the large accumulations observed in the mesenteries and ascites fluid of tumor-bearing animals most likely resulted from increased synthesis and secretion by peritoneal-lining mesothelial cells and/or fibroblasts in response to stimulation by the tumor cells or their products. TA3/St tumor cells were universally positive for the hyaluronan receptor, CD44, whereas approximately 90% of MOT tumor cells were CD44-negative. However, the great majority of MOT or TA3/St cells that initially attached to the mesentery were strongly CD44 positive. We propose that hyaluronan-rich matrix is involved in tumor cell attachment to the mesentery possibly via interaction with tumor cell surface CD44.

 

PMID: 8669459 [PubMed - indexed for MEDLINE]

 

[v] Int J Cancer. 2002 Nov 10;102(2):192-7.

Hyaluronidase reduces human breast cancer xenografts in SCID mice.

Shuster S, Frost GI, Csoka AB , Formby B, Stern R.

 

Department of Pathology, School of Medicine, University of California San Francisco, San Francisco, CA 94143-0511, USA.

 

A hyaluronan-rich environment often correlate with tumor progression. and may be one mechanism for the invasive behavior of malignancies. Eradication of hyaluronan by hyaluronidase administration could reduce tumor aggressiveness and would provide, therefore, a new anti-cancer strategy. Hyaluronan interaction with its CD44 receptor and the resulting signal transduction events may be among the mechanisms for hyaluronan-associated cancer progression. We have shown previously that hyaluronidase treatment of breast cancer cells in vitro not only eradicates hyaluronan but also modifies expression of CD44 variant exons of tumor cells. We now determine if such effects occur in vivo and if it is accompanied by tumor regression. SCID mice bearing xenografts of human breast carcinomas were given intravenous hyaluronidase. Tumor volumes decreased 50% in 4 days. Tumor sections showed decreased hyaluronan. Intensity of staining for CD44s was not affected, whereas staining for specific CD44 variant exon isoforms was greatly reduced in residual tumors. Necrosis was not evident. Hyaluronidase, used previously as an adjunct in cancer treatment, presumably to enhance penetration of chemotherapeutic drugs, may itself have intrinsic anti-cancer activity. Removing peritumor hyaluronan appears to cause an irreversible change in tumor metabolism. Continuous hyaluronan binding to CD44 variant exon isoforms may also be required to stabilize inherently unstable isoforms that participate perhaps in tumor progression. Further investigation is required to confirm a cause and effect relationship between loss of hyaluronan, changes in CD44 variant exon expression and tumor reduction. If confirmed, hyaluronidase may provide a new class of anti-cancer therapeutics and one without toxic side effects. Copyright 2002 Wiley-Liss, Inc.

 

PMID: 12385018 [PubMed - indexed for MEDLINE]

 

[vi] J Cancer Res Clin Oncol. 1992;118(8):591-6

Hyaluronidase enhances the activity of adriamycin in breast cancer models in vitro and in vivo.

Beckenlehner K, Bannke S, Spruss T, Bernhardt G, Schonenberg H, Schiess W.

 

Institut fur Pharmazie, Universitat Regensburg, Federal Republic of Germany.

 

The effect of hyaluronidase and a combination of hyaluronidase with Adriamycin was investigated on several breast cancer models in vitro and in vivo. In vitro enzyme treatment (using concentrations up to 80,000 IU/1) of murine (MXT-, MXT +/-, and MXT+) and human (MCF-7, ZR-75-1 and T-47-D) breast cancer cell lines did not inhibit tumour cell proliferation (measured by a kinetic crystal violet assay) in either case. Although high-dose hyaluronidase (1.2 x 10(6) IU/kg) was ineffective, when administered peritumourally to the MXT M3.2 mammary carcinoma of the B6D2F1 mouse, it is remarkable that five "megadoses" were excellently tolerated. However, the antineoplastic activity of Adriamycin against the oestrogen-receptor-positive variant of the MXT tumour was significantly enhanced by combination with concentrations of hyaluronidase that were inactive per se, both in vitro and in vivo. Interestingly, the enhancement of the in vivo antitumour activity was not compromised by toxic side-effects.

 

PMID: 1517281 [PubMed - indexed for MEDLINE]

 

[vii] Exp Mol Pathol. 2002 Jun;72(3):179-85.

Effect of hyaluronan on xenotransplanted breast cancer.

Herrera-Gayol A, Jothy S.

 

Department of Pathology, McGill University , Montreal , Quebec , Canada .

 

Hyaluronan is a major glycosaminoglycan component of the extracellular matrix and CD44 is its principal ligand. In previous in vitro studies we have shown that CD44 and hyaluronan are involved in the invasive properties of the human breast cancer cell line Hs578T. The aim of this study was to test whether experimental therapy with hyaluronan interferes with tumor invasion and has an inhibitory effect on tumor growth in vivo. The Hs578T cell line was xenotransplanted orthotopically into the mammary fat pad of nu/nu mice. After tumor growth reached a maximum size of 5 x 5 mm, 50 microg of hyaluronan was injected intratumorally. The tumors of control nu/nu mice were injected with PBS. Four of 12 tumors from the hyaluronan-treated group regressed completely. This effect could be due to a saturation of the hyaluronan-binding sites on tumor cells or to an acceleration of tumor rejection by a non-T-cell-dependent mechanism. This study gives a rationale for future work on the antineoplastic effects of hyaluronan.

 

PMID: 12009781 [PubMed - indexed for MEDLINE]

[viii] Am J Pathol. 1996 Jun;148(6):1733-40.

Increased hyaluronan at sites of attachment to mesentery by CD44-positive mouse ovarian and breast tumor cells.

Yeo TK, Nagy JA, Yeo KT, Dvorak HF, Toole BP.

 

Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston , MA 02111 , USA .

 

The mouse ovarian ascites tumor, MOT, and mammary ascites tumor, TA3/St, served as models to follow changes in hyaluronan levels during tumor growth, attachment, and invasion. Subsequent to introduction of tumor cells into the peritoneal cavity, hyaluronan accumulated intraperitoneally and at the initial sites of attachment of tumor cells and cell clumps to the mesenteric surface; the latter co-localized with sites of fibrin deposition as reported earlier. Subsequently, high levels of hyaluronan accumulated throughout the interior of the mesentery. Because neither tumor cell line synthesized substantial amounts of hyaluronan in culture, the large accumulations observed in the mesenteries and ascites fluid of tumor-bearing animals most likely resulted from increased synthesis and secretion by peritoneal-lining mesothelial cells and/or fibroblasts in response to stimulation by the tumor cells or their products. TA3/St tumor cells were universally positive for the hyaluronan receptor, CD44, whereas approximately 90% of MOT tumor cells were CD44-negative. However, the great majority of MOT or TA3/St cells that initially attached to the mesentery were strongly CD44 positive. We propose that hyaluronan-rich matrix is involved in tumor cell attachment to the mesentery possibly via interaction with tumor cell surface CD44.

 

PMID: 8669459 [PubMed - indexed for MEDLINE]

[ix] J Cell Physiol. 1994 Aug;160(2):275-86.

Binding and degradation of hyaluronan by human breast cancer cell lines expressing different forms of CD44: correlation with invasive potential.

Culty M, Shizari M, Thompson EW, Underhill CB.

 

Department of Cell Biology, Georgetown University Medical Center , Washington , D.C. 20007.

 

In the present study, we examined a panel of human breast cancer cell lines with regard to their expression of CD44 and ability to bind and degrade hyaluronan. The cell lines expressed varying amounts of different molecular weight forms of CD44 (85-200 kDa) and, in general, those that expressed the greatest amounts of CD44 were the most invasive as judged by in vitro assays. In addition, the ability to bind and degrade hyaluronan was restricted to the cell lines expressing high levels of CD44, and both these functions were blocked by an antibody to CD44 (Hermes-1). Moreover, the rate of [3H]hyaluronan degradation was highly correlated with the amount of CD44 (r = 0.951, P < 0.0001), as well as with the invasive potential of the cells. Scatchard analysis of the [3H]hyaluronan binding of these cells revealed the existence of significant differences in both their binding capacity and their dissociation constant. To determine the source of this deviation, the different molecular weight forms of CD44 were partially separated by gel filtration chromatography. In all cell lines, the 85 kDa form was able to bind hyaluronan, although with different affinities. In contrast, not all of the high molecular weight forms of CD44 had this ability. These results illustrate the diversity of CD44 molecules in invasive tumor cells, and suggest that one of their major functions is to degrade hyaluronan.

 

[x] J Int Med Res. 2000 Mar-Apr;28(2):78-90.

Expression of CD44 variants in lung cancer and its relationship to hyaluronan binding.

Matsubara Y, Katoh S, Taniguchii H, Oka M, Kadota J, Kohno S.

 

Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan .

 

We examined the expression of CD44 variant forms and their binding to hyaluronan (HA) in lung cancer cell lines. There was no relationship between the level of expression of CD44 variants and HA binding in different lung cancer cell lines. The expression of CD44v6 and CD44E in some cell lines was not always associated with HA binding. There was no relationship between the tissue pathological type and CD44 expression or HA binding. Deglycosylation by neuraminidase induced CD44-HA binding in human lung cancer cell lines. Our findings suggest that the HA binding ability of CD44, which is negatively regulated by glycosylation, might be a more important factor in tumorigenesis or metastasis than the expression of CD44 variant forms.

 

PMID: 10898120 [PubMed - indexed for MEDLINE]

 

[xi] Cancer Res. 2002 Nov 15;62(22):6410-3.

Elevated hyaluronan concentration without hyaluronidase activation in malignant epithelial ovarian tumors.

Hiltunen EL, Anttila M, Kultti A, Ropponen K, Penttinen J, Yliskoski M, Kuronen AT, Juhola M, Tammi R, Tammi M, Kosma VM.

 

Department of Pathology and Forensic Medicine, University of Kuopio and Kuopio University Hospital , 70211 Kuopio , Finland .

 

The concentration and histological distribution of hyaluronan, a tumor promoting extracellular matrix polysaccharide, and the activity of hyaluronidase, a potential source of angiogenic hyaluronan oligosaccharides, were analyzed in malignant epithelial (n = 24), borderline (n = 8), benign epithelial (n = 20), functional cyst (n = 21), and normal (n = 5) tissue samples of human ovary. Hyaluronan concentration increased specifically in cancers (P = 0.001), particularly in grade 3 tumors (>49-fold) and in metastases (>89-fold). Hyaluronan staining in the tissues correlated with hyaluronan concentration (P = 0.002). Hyaluronidase activity slightly decreased from semimalignant through low grade to high grade tumors (P = 0.041). Therefore, hyaluronan accumulation, but not hyaluronidase activation, is associated with the aggressiveness of ovarian epithelial cancer.

 

PMID: 12438225 [PubMed - indexed for MEDLINE]

 

[xii] J Exp Med. 1997 Dec 15;186(12):1985-96.

Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function.

Yu Q, Toole BP, Stamenkovic I.

 

Molecular Pathology Unit and MGH Cancer Center, Massachusetts General Hospital, Charlestown Navy Yard, Boston, Massachusetts 02129, USA.

 

To understand how the hyaluronan receptor CD44 regulates tumor metastasis, the murine mammary carcinoma TA3/St, which constitutively expresses cell surface CD44, was transfected with cDNAs encoding soluble isoforms of CD44 and the transfectants (TA3sCD44) were compared with parental cells (transfected with expression vector only) for growth in vivo and in vitro. Local release of soluble CD44 by the transfectants inhibited the ability of endogenous cell surface CD44 to bind and internalize hyaluronan and to mediate TA3 cell invasion of hyaluronan-producing cell monolayers. Mice intravenously injected with parental TA3/St cells developed massive pulmonary metastases within 21-28 d, whereas animals injected with TA3sCD44 cells developed few or no tumors. Tracing of labeled parental and transfectant tumor cells revealed that both cell types initially adhered to pulmonary endothelium and penetrated the interstitial stroma. However, although parental cells were dividing and forming clusters within lung tissue 48 h following injection, >80% of TA3sCD44 cells underwent apoptosis. Although sCD44 transfectants displayed a marked reduction in their ability to internalize and degrade hyaluronan, they elicited abundant local hyaluronan production within invaded lung tissue, comparable to that induced by parental cells. These observations provide direct evidence that cell surface CD44 function promotes tumor cell survival in invaded tissue and that its suppression can induce apoptosis of the invading tumor cells, possibly as a result of impairing their ability to penetrate the host tissue hyaluronan barrier.

 PMID: 9396767 [PubMed - indexed for MEDLINE]

 

[xiii] Int J Cancer. 1998 Jul 29;77(3):396-401.

Inhibition of tumor growth in vivo by hyaluronan oligomers.

Zeng C, Toole BP, Kinney SD, Kuo JW, Stamenkovic I.

 

Department of Pathology, Harvard Medical School, and Pathology Research Laboratories, Massachusetts General Hospital, Boston 02129, USA.

 

One of the critical events in tumor growth and metastasis is the interaction between tumor cells and host tissue stroma, mediated by different adhesion receptor repertoires in different tumor cell types. Several lines of evidence indicate that interaction between the hyaluronan receptor CD44, expressed on tumor cells, and host tissue stromal hyaluronan can enhance growth and invasiveness of certain tumors. Disruption of CD44-hyaluronan interaction by soluble recombinant CD44 has been shown to inhibit tumor formation by lymphoma and melanoma cells transfected with CD44. Since hyaluronan is a ubiquitous glycosaminoglycan polymer from which oligosaccharides of defined size can be readily purified, we tested the ability of hyaluronan oligomers to inhibit tumor formation by subcutaneously ( s.c. ) injected B16F10 melanoma cells. Our results indicate that hyaluronan oligomers injected at concentrations as low as 1 mg/ml can markedly inhibit B16F10 melanoma growth, providing a potentially attractive reagent for the control of local tumor development.

 

PMID: 9663602 [PubMed - indexed for MEDLINE]

 


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