Growth regulated oncogene-α expression by murine squamous cell carcinoma promotes tumor growth, metastasis, leukocyte infiltration and angiogenesis by a host CXC receptor-2 dependent mechanism

Elena Loukinova, Gang Dong, Ileana Enamorado-Ayalya, Giovana R. Thomas, Zhong Chen, Hans Schreiber, Carter Van Waes

Research output: Contribution to journalArticle

151 Scopus citations

Abstract

Growth Regulated Oncogene-α (GRO-α) is an autocrine growth factor in melanoma and is a member of the C-X-C family of chemokines which promote chemotaxis of granulocytes and endothelia through binding to CXC Receptor 2. We found previously that variants of murine squamous cell carcinoma PAM 212 which grow and metastasize more rapidly in vivo constitutively express increased levels of murine GRO-α, designated mGRO-α, or KC. We have examined the possible role of mGRO-α expression in malignant progression of squamous cell carcinoma PAM 212 in homologous BALB/c and BALB CXC Receptor-2. deficient mice. Transfection of the PAM 212 cell line which exhibits low expression of GRO-α and malignant potential with a pActin-KC vector encoding mGRO-α enabled isolation of PAM-KC expressing cell lines. These PAM-KC transfectants displayed an increased rate of growth and metastasis in BALB/c mice, similar to the highly malignant phenotype observed in spontaneously occurring metastatic variants. Furthermore, the PAM-KC tumors showed an increase in infiltration of host leukocytes and CD31+ blood vessels, consistent with increased CXC chemokine activity. The increased growth of PAM-KC cells was attenuated in CXCR-2 deficient mice, indicating that the increased growth was dependent in part upon host tells responsive to the CXC chemokine. Together, these results show that a CXC chemokine such as GRO-α can promote malignant growth of murine squamous cell carcinoma hg a host CXCR-2 dependent pathway.

Original languageEnglish (US)
Pages (from-to)3477-3486
Number of pages10
JournalOncogene
Volume19
Issue number31
DOIs
StatePublished - Jul 20 2000
Externally publishedYes

Keywords

  • Chemokines
  • CXCR2
  • GRO-α
  • KC
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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