Hyaluronidase gene profiling and role of hyal-1 overexpression in an orthotopic model of prostate cancer.
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.
Patel
Sonal
S
Oxford GlycoSciences, Abingdon Science Park, Abingdon, Oxfordshire, United Kingdom.
Turner
Paul R
PR
Stubberfield
Colin
C
Barry
Eleanor
E
Rohlff
Christian R
CR
Stamps
Alasdair
A
McKenzie
Edward
E
Young
Kathryn
K
Tyson
Kerry
K
Terrett
Jon
J
Box
Gary
G
Eccles
Suzanne
S
Page
Martin J
MJ
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001940:Breast / Q000201:enzymology; D001943:Breast Neoplasms / Q000097:blood / Q000201:enzymology; D004790:Enzyme Induction; D005260:Female; D020869:Gene Expression Profiling; D005796:Genes; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D005810:Multigene Family; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000032:analysis; D013347:Subcellular Fractions / Q000201:enzymology; D013737:Testis / Q000201:enzymology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000201:enzymology
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D006821:Hyaluronoglucosaminidase