Down-regulation of CXCL5 inhibits squamous carcinogenesis

Hiroshi Miyazaki, Vyomesh Patel, Huixin Wang, Ryan K. Edmunds, J. Silvio Gutkind, W. Andrew Yeudall

Research output: Contribution to journalArticle

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Abstract

We report a novel role for the CXC-chemokine, CXCL5, in the proliferation and invasion of head and neck squamous cell carcinoma (HNSCC). Previously, we reported transcriptional up-regulation of CXCL5 in metastatic cells. In this study, we provide biological validation of these findings and show that CXCL5 is intimately involved in tumor cell proliferation, migration, and invasion. Cells derived from a lymph node metastasis, but not from a synchronous primary tumor, secreted CXCL5 as judged by Western blotting of conditioned media. We used RNA interference to generate cell lines (shL5) in which CXCL5 expression was greatly reduced, and tested whether this modulated the cell phenotype. shL5 cells showed decreased proliferation compared with cells harboring non-targeting control sequences. In addition, we found that the ability of shL5 cells to migrate and invade in vitro through a basement membrane substitute was greatly impaired compared with control cells. Finally, whereas control cells were highly tumorigenic in nude mice, the tumorigenic potential in vivo of shL5 cells was found to be ablated. Taken together, these data suggest that CXCL5 production contributes to both enhanced proliferation and invasion of squamous cell carcinomas and that targeting of chemokine pathways may represent a potential therapeutic modality for these lesions.

Original languageEnglish (US)
Pages (from-to)4279-4284
Number of pages6
JournalCancer Research
Volume66
Issue number8
DOIs
StatePublished - Apr 15 2006

Fingerprint

Carcinogenesis
Down-Regulation
Chemokine CXCL5
CXC Chemokines
Conditioned Culture Medium
RNA Interference
Chemokines
Basement Membrane
Nude Mice
Cell Movement
Squamous Cell Carcinoma
Neoplasms
Up-Regulation
Lymph Nodes
Western Blotting
Cell Proliferation
Neoplasm Metastasis
Phenotype
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Miyazaki, H., Patel, V., Wang, H., Edmunds, R. K., Gutkind, J. S., & Yeudall, W. A. (2006). Down-regulation of CXCL5 inhibits squamous carcinogenesis. Cancer Research, 66(8), 4279-4284. https://doi.org/10.1158/0008-5472.CAN-05-4398

Down-regulation of CXCL5 inhibits squamous carcinogenesis. / Miyazaki, Hiroshi; Patel, Vyomesh; Wang, Huixin; Edmunds, Ryan K.; Gutkind, J. Silvio; Yeudall, W. Andrew.

In: Cancer Research, Vol. 66, No. 8, 15.04.2006, p. 4279-4284.

Research output: Contribution to journalArticle

Miyazaki, H, Patel, V, Wang, H, Edmunds, RK, Gutkind, JS & Yeudall, WA 2006, 'Down-regulation of CXCL5 inhibits squamous carcinogenesis', Cancer Research, vol. 66, no. 8, pp. 4279-4284. https://doi.org/10.1158/0008-5472.CAN-05-4398
Miyazaki H, Patel V, Wang H, Edmunds RK, Gutkind JS, Yeudall WA. Down-regulation of CXCL5 inhibits squamous carcinogenesis. Cancer Research. 2006 Apr 15;66(8):4279-4284. https://doi.org/10.1158/0008-5472.CAN-05-4398
Miyazaki, Hiroshi ; Patel, Vyomesh ; Wang, Huixin ; Edmunds, Ryan K. ; Gutkind, J. Silvio ; Yeudall, W. Andrew. / Down-regulation of CXCL5 inhibits squamous carcinogenesis. In: Cancer Research. 2006 ; Vol. 66, No. 8. pp. 4279-4284.
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