Modulation of CXCL-8 expression in human melanoma cells regulates tumor growth, angiogenesis, invasion, and metastasis.
CXCL-8, a chemokine secreted by melanoma and stromal cells, serves as a growth and angiogenic factor for melanoma progression. This study evaluated how modulation of CXCL-8 levels in melanoma cell lines with different tumorigenic and metastatic potentials affected multiple tumor phenotypes. A375P cells (CXCL-8 low expressor) were stably transfected with a CXCL-8 mammalian expression vector to overexpress CXCL-8, whereas A375SM cells (CXCL-8 high expressor) were transfected with a CXCL-8 antisense expression vector to suppress CXCL-8 expression. Subsequent cell proliferation, migration, invasion, and soft-agar colony formation were analyzed, and in vivo tumor growth and metastasis were evaluated using mouse xenograft models. Our data demonstrate that overexpression of CXCL-8 significantly enhanced primary tumor growth and lung metastasis, accompanied by increased microvessel density in vivo, as compared with vector control-transfected cells. We also observed increased clonogenic ability, growth, and invasive potential of CXCL-8 overexpressing cells in vitro. Knockdown of CXCL-8 using an antisense vector resulted in increased cell death and reduced tumor growth relative to control. Taken together, these data confirm that CXCL-8 expression plays a critical role in regulating multiple cellular phenotypes associated with melanoma growth and metastasis.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Sheng
S
Wu
Seema
S
Singh
Michelle L
ML
Varney
Scott
S
Kindle
Rakesh K
RK
Singh
D000818:Animals; D063646:Carcinogenesis; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic; D017154:Stromal Cells / Q000473:pathology
C508606:CXCL8 protein, human; D016209:Interleukin-8
Angiogenesis; CXCL-8; melanoma; metastasis; proliferation