EphA2 overexpression promotes ovarian cancer growth.
BACKGROUND
Silencing EphA2 has been shown to result in anti-tumor efficacy. However, it is not known whether increasing EphA2 expression specifically results in increased tumor growth and progression. We examined the effects of stable EphA2 transfection into poorly invasive ovarian cancer cells with regard to in vitro invasive and in vivo metastatic potential.


RESULTS
In low cell density, EphA2-overexpressing A2780 cells (A2780-EphA2) displayed less cell-cell contact, increased cell-extracellular matrix (ECM) attachment and anchorage-independent cell growth compared to empty vector controls. There was no significant effect on anchorage-dependent cell proliferation, migration or invasion. Increased expression of EphA2 promoted tumor growth and enhanced the metastatic potential in A2780-EphA2 human ovarian cancer xenografts. The overexpression of EphA2 resulted in enhanced microvessel density (MVD), but had no effect on tumor cell proliferation.


METHODS
EphA2 gene was introduced into A2780 cells by retroviral infection. The effects of increased EphA2 expression were examined on cellular morphology, and anchorage-dependent and independent cell growth. Furthermore, the effect of EphA2 overexpression on metastatic ability was determined using an orthotopic nude mouse model of ovarian carcinoma.


CONCLUSIONS
EphA2 promotes tumor growth by enhancing cell-ECM adhesion, increasing anchorage-independent growth and promoting angiogenesis.
Lu
Chunhua
C
Department of Gynecologic Oncology, U.T.M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Shahzad
Mian M K
MM
Wang
Hua
H
Landen
Charles N
CN
Kim
Seung W
SW
Allen
Julie
J
Nick
Alpa M
AM
Jennings
Nicholas
N
Kinch
Michael S
MS
Bar-Eli
Menashe
M
Sood
Anil K
AK
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000378:metabolism*; D036104:Receptor, EphA2 / Q000096:biosynthesis* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D036104:Receptor, EphA2; D020782:Matrix Metalloproteinases