Role for β3 integrins in human melanoma growth and survival

Mohit Trikha, J. Tímár, Alex Zacharek, Jeffrey A. Nemeth, Yinlong Cai, B. Döme, B. Somlai, E. Rásó, A. Ladányi, Kenneth V. Honn

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The role of αIIbβ3 integrin in regulating platelet function is well appreciated, whereas its role in tumor progression and metastasis is not. The purpose of our study was to determine a functional relevance to expression of αIIbβ3 integrin in cells derived from human solid tumors. A study of human melanoma biopsies (n = 24) showed that αIIbβ3 expression increased with tumor thickness, which is indicative of metastatic propensity. Expression of αIIbβ3 was 8% (±1.8), 33% (±10.4) and 62% (±5) in melanomas ranging in thickness from 0-1.5 mm, 1.5-4.0 mm and >4 mm, respectively; αvβ3 was equally high all categories. To determine biological function, we stably transfected αIIbβ3 into human melanoma cells that express αvβ3, but not αIIbβ3. Surface expression of αvβ3 remained unaltered between αIIbβ3 (+) and mock transfected counterparts. The αIIbβ3 (+) cells possessed increased ability to adhere, spread and migrate on fibrinogen. They had decreased ability to attach, spread and migrate on vitronectin. Immunocytochemistry showed that expression of αIIbβ3 displaced αvβ3 from focal contact points. When implanted subcutaneously into SCID mice, the αIIbβ3 (+) cells developed ∼4-fold larger tumors when compared to their mock counterparts and the level of apoptosis was reduced within the tumors. Results suggest that co-expression of the 2 β3 integrins, αvβ3 and αIIbβ3, in human melanoma cells enhanced cell survival and promoted growth in vivo.

Original languageEnglish
Pages (from-to)156-167
Number of pages12
JournalInternational Journal of Cancer
Volume101
Issue number2
DOIs
Publication statusPublished - Sep 10 2002

Fingerprint

Integrins
Melanoma
Survival
Growth
Neoplasms
Vitronectin
Focal Adhesions
SCID Mice
Fibrinogen
Cell Survival
Blood Platelets
Immunohistochemistry
Apoptosis
Neoplasm Metastasis
Biopsy

Keywords

  • α@vβ3
  • GPIIb/IIIa
  • Growth
  • Integrin
  • Tumor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Role for β3 integrins in human melanoma growth and survival. / Trikha, Mohit; Tímár, J.; Zacharek, Alex; Nemeth, Jeffrey A.; Cai, Yinlong; Döme, B.; Somlai, B.; Rásó, E.; Ladányi, A.; Honn, Kenneth V.

In: International Journal of Cancer, Vol. 101, No. 2, 10.09.2002, p. 156-167.

Research output: Contribution to journalArticle

Trikha, Mohit ; Tímár, J. ; Zacharek, Alex ; Nemeth, Jeffrey A. ; Cai, Yinlong ; Döme, B. ; Somlai, B. ; Rásó, E. ; Ladányi, A. ; Honn, Kenneth V. / Role for β3 integrins in human melanoma growth and survival. In: International Journal of Cancer. 2002 ; Vol. 101, No. 2. pp. 156-167.
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