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Hyaluronidase gene profiling and role of HYAL‐1 overexpression in an orthotopic model of prostate cancer
Author(s) -
Patel Sonal,
Turner Paul R.,
Stubberfield Colin,
Barry Eleanor,
Rohlff Christian R.,
Stamps Alasdair,
Tyson Kerry,
Terrett Jon,
Box Gary,
Eccles Suzanne,
Page Martin J.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1638
Subject(s) - hyaluronidase , prostate cancer , cell culture , cancer research , breast cancer , biology , prostate , metastasis , pathology , cancer , microbiology and biotechnology , medicine , enzyme , biochemistry , genetics
The mRNA levels of hyal‐1, hyal‐2, LUCA3 and PH20, the 4 hyaluronidases with demonstrated endoglucosaminidase activity, were extensively profiled in normal and tumor tissues and cell lines, using dot blot analysis and quantitative PCR. In normal tissues, hyal‐1, hyal‐2 and LUCA3 all showed unique patterns of mRNA expression, but were generally of widespread distribution, whereas PH20 mRNA was restricted to testes. In a small set of breast tumor samples, no elevations in hyal‐1, hyal‐2 or LUCA3 mRNA were seen. Hyaluronidase activity measured by a novel assay or zymography was also not elevated in sera from a number of breast cancer patients, compared to sera from normal volunteers. In ex vivo xenograft tumor cell lines, however, hyal‐1 or hyal‐2 mRNA levels were frequently elevated, whereas LUCA3 was only infrequently elevated and PH20 not at all. Two cell lines were engineered to overexpress hyal‐1: a breast cancer line (CAL51) and a prostate cancer line (PC3M). Although the in vitro properties of the hyal‐1 overexpressing cell lines were indistinguishable from the parental cells, the orthotopic growth of hyal‐1 expressing PC3M cells in nu / nu mice resulted in significantly increased numbers of metastases, supportive of a role for hyal‐1 in extravasation and metastatic tumor formation in this model of prostate cancer. © 2001 Wiley‐Liss, Inc.