Uncoupling of epidermal growth factor-dependent proliferation and invasion in a model of squamous carcinoma progression

William Andrew Yeudall, Hiroshi Miyazaki, John F. Ensley, Massimo Cardinali, J. Silvio Gutkind, Vyomesh Patel

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Cell lines pairs were established from a primary squamous carcinoma of tongue and a lymph node metastasis and their biological behavior characterized. HN12 cells, derived from metastatic SCC, formed tumors upon subcutaneous transplantation to athymic mice, whereas HN4, derived from a primary lesion in the same individual, were non-tumorigenic in this assay. EGF stimulated proliferation of HN4 cells; in comparison, not only were metastatic HN12 cells refractory to the stimulatory effects of this growth factor but showed inhibition at higher growth factor concentrations. However, in contrast to the effects on proliferation, EGF (10 ng/ml) readily induced HN12 cells to invade in Boyden chamber assays whereas HN4 were non-invasive under these conditions. The invasive properties of HN12 cells were apparently independent of MMP-2 activity, as levels of active MMP-2 were higher in the non-invasive cells. However, EGF stimulated MMP-9 activity in invasive cells. Additionally, HN12 cells expressed constitutively high levels of active MMP-7 and MMP-3/10. The pharmacological agents LY294002, PD098059, SP600125, or SB202190 inhibited invasion of HN12 cells, suggesting requirement for phosphoinositide 3-OH kinase- and mitogen activated protein kinase-dependent pathways in the process. The data indicate that distinct biochemical differences distinguish metastatic squamous carcinoma cells from those derived from corresponding primary tumors, resulting in their contrasting biological properties.

Original languageEnglish (US)
Pages (from-to)698-708
Number of pages11
JournalOral Oncology
Issue number7
StatePublished - Aug 2005
Externally publishedYes


  • Growth factor
  • Invasion
  • Metastasis
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research


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