Heparanase promotes growth, angiogenesis and survival of primary breast tumors

Irit Cohen, Orit Pappo, Michael Elkin, Tamara San, Rachel Bar-Shavit, Rachel Hazan, Tamar Peretz, Israel Vlodavsky, Rinat Abramovitch

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Despite great strides toward diagnosis and therapy, breast cancer remains a most threatening disease in its incidence, morbidity and mortality; therefore, additional knowledge regarding the molecular mechanisms contributing to breast cancer progression, as well as new targets for drug discovery are highly needed. Heparanase is the predominant enzyme involved in cleavage of heparan sulfate, the main polysaccharide component of the extracellular matrix. Experimental and clinical data indicate that heparanase plays important roles in cancer metastasis and angiogenesis. In breast carcinoma patients, heparanase expression correlates with the metastatic potential of the tumor. The present study was undertaken to investigate the role of heparanase in local growth and angiogenesis of primary breast tumors. MCF-7 breast carcinoma cells were stable transfected with the human heparanase (H-hpa) cDNA, or empty vector (mock), and injected into the mammary pad of nude mice. MRI was applied to monitor progression of tumor growth and angiogenesis. We demonstrate that tumors produced by cells overexpressing heparanase grew faster and were 7-fold larger than tumors produced by mock transfected cells. This enhanced growth was accompanied by increased tumor vascularization and a higher degree of vessel maturation. Histological examination ascribed the differences in tumor growth to heparanase-stimulated cell proliferation and survival. In-vitro experiments reinforced heparanase role as a survival factor under stress conditions. Moreover, H-hpa tumor cells infiltrate into the adjacent stroma, promoting formation of highly vascularized fibrous bands. Our results emphasize the significance and clarify the involvement of heparanase in primary breast cancer progression by generating a supportive microenvironment that promotes tumor growth, angiogenesis and survival.

Original languageEnglish (US)
Pages (from-to)1609-1617
Number of pages9
JournalInternational Journal of Cancer
Volume118
Issue number7
DOIs
StatePublished - Apr 1 2006

Fingerprint

Breast Neoplasms
Survival
Growth
Neoplasms
heparanase
Tumor Microenvironment
Heparitin Sulfate
Drug Discovery
Nude Mice
Extracellular Matrix
Polysaccharides
Cell Survival
Breast
Complementary DNA
Cell Proliferation
Neoplasm Metastasis
Morbidity
Mortality
Incidence
Enzymes

Keywords

  • Angiogenesis
  • Apoptosis
  • Heparanase
  • MRI
  • Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cohen, I., Pappo, O., Elkin, M., San, T., Bar-Shavit, R., Hazan, R., ... Abramovitch, R. (2006). Heparanase promotes growth, angiogenesis and survival of primary breast tumors. International Journal of Cancer, 118(7), 1609-1617. https://doi.org/10.1002/ijc.21552

Heparanase promotes growth, angiogenesis and survival of primary breast tumors. / Cohen, Irit; Pappo, Orit; Elkin, Michael; San, Tamara; Bar-Shavit, Rachel; Hazan, Rachel; Peretz, Tamar; Vlodavsky, Israel; Abramovitch, Rinat.

In: International Journal of Cancer, Vol. 118, No. 7, 01.04.2006, p. 1609-1617.

Research output: Contribution to journalArticle

Cohen, I, Pappo, O, Elkin, M, San, T, Bar-Shavit, R, Hazan, R, Peretz, T, Vlodavsky, I & Abramovitch, R 2006, 'Heparanase promotes growth, angiogenesis and survival of primary breast tumors', International Journal of Cancer, vol. 118, no. 7, pp. 1609-1617. https://doi.org/10.1002/ijc.21552
Cohen, Irit ; Pappo, Orit ; Elkin, Michael ; San, Tamara ; Bar-Shavit, Rachel ; Hazan, Rachel ; Peretz, Tamar ; Vlodavsky, Israel ; Abramovitch, Rinat. / Heparanase promotes growth, angiogenesis and survival of primary breast tumors. In: International Journal of Cancer. 2006 ; Vol. 118, No. 7. pp. 1609-1617.
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