Selective heparanase localization in malignant melanoma.
Heparanase (HPSE-1) is an endo-beta-D-glucuronidase that cleaves heparan sulfate proteoglycans (HSPG), and its expression has been associated with increased growth, metastasis, and angiogenesis of tumors. Since metastatic melanoma cells express high levels of HSPG and because melanoma tumors grow highly vascularized, we analyzed melanoma tissue specimens for HPSE-1 expression from experimental animals as well as from patients. Laser capture microdissection microscopy was used to extract melanoma cell populations and to isolate them from adjacent tissue. In experimental animals, a 29-fold upregulation of HPSE-1 expression was detected by real-time PCR in metastatic melanoma compared to normal lung tissue. Additionally, immunohistochemistry (IHC) revealed selective HPSE-1 staining in human metastatic melanoma when compared to primary melanoma tumors from the same patient. IHC also showed a marked staining for the enzyme around blood vessels and in vascularized regions. Our results provide evidence demonstrating that HPSE-1 likely plays important roles in regulating the in vivo growth and progression of melanoma. These results further emphasize the importance that therapies designed to block HPSE-1 activity may aid in controlling this type of cancer.
Murry
Brian P
BP
Department of Comparative Biomedical Sciences, Louisiana State University-Baton Rouge, Baton Rouge, LA 70803, USA.
Greiter-Wilke
Andrea
A
Paulsen
Daniel P
DP
Hiatt
Kim M
KM
Beltrami
Carlo Alberto
CA
Marchetti
Dario
D
D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008168:Lung / Q000473:pathology; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism; D009389:Neovascularization, Pathologic; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation; D000099175:Heparanase
D017931:DNA Primers; D018076:DNA, Complementary; D005966:Glucuronidase; D012313:RNA; D012333:RNA, Messenger; D000099175:Heparanase