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Bioidentical Hormones - U.S. Senate Special Committee on Aging

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125<br />

|Hyalur<strong>on</strong>idase c molate I E;<br />

. Stern R,<br />

• Shuster S,<br />

* Wiley TS,<br />

. Formby S.<br />

Department of Pathology, School of Medicine, University of California, San Francisco,<br />

California 94143-0506, USA. rstern@itsa.ucsf.edi<br />

CD44 is a family of transmembrane glycoproteins with multiple isoforms<br />

generated by alternative ex<strong>on</strong> splicing of a single gene. CD44 and its variants<br />

are expressed <strong>on</strong> a wide variety of cells including cancer cells. The mechanisms<br />

by which splice variant ex<strong>on</strong>s are selected are unknown. The presence of<br />

hyalur<strong>on</strong>an in the envir<strong>on</strong>ment of the cell appears to influence that selecti<strong>on</strong><br />

process. The expressi<strong>on</strong> of particular splice variants of CD44 as well as the<br />

simultaneous presence of hyalur<strong>on</strong>an Is Important for motility, Invasi<strong>on</strong>, and the<br />

metastatic spread of some tumors. The influence of hyalur<strong>on</strong>idase digesti<strong>on</strong> <strong>on</strong><br />

the expressi<strong>on</strong> of CD44 in human cancer cell lines was examined. CD44 Isoforms<br />

c<strong>on</strong>taining alternatively spliced ex<strong>on</strong>s were sensitive to hyalur<strong>on</strong>idase digesti<strong>on</strong><br />

In all lines examined, but differences between cell lines were observed.<br />

Expressi<strong>on</strong> of CD44s, the standard form, was resistant to digesti<strong>on</strong> in two of<br />

three cell lines. A tentative model was formulated proposing that CD44 Isoforms<br />

c<strong>on</strong>taining splice variants are unstable, requiring the c<strong>on</strong>tinuous presence of<br />

li.arnd fv ur pressirl. CD44s is reiativeiy more stable, not requiring the<br />

c<strong>on</strong>tinuous presence of hyalur<strong>on</strong>an. Additi<strong>on</strong>ally, a number of new CD44 variant<br />

isoforms, not previously observed, were identified. Copyright 2001 Academic<br />

Press.<br />

PMID: 11339835 [PubMed - Indexed foe MEDLINE]

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