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 journalArticle

21 Citations (Scopus)

Abstract

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
Volume41
Issue number7
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Squamous Cell Carcinoma
Matrix Metalloproteinases
Intercellular Signaling Peptides and Proteins
MAP Kinase Kinase 3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Phosphatidylinositols
Tongue
Nude Mice
Neoplasms
Transplantation
Lymph Nodes
Cell Proliferation
Pharmacology
Neoplasm Metastasis
Cell Line

Keywords

  • Growth factor
  • Invasion
  • Metastasis
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

Cite this

Uncoupling of epidermal growth factor-dependent proliferation and invasion in a model of squamous carcinoma progression. / Yeudall, William Andrew; Miyazaki, Hiroshi; Ensley, John F.; Cardinali, Massimo; Gutkind, J. Silvio; Patel, Vyomesh.

In: Oral Oncology, Vol. 41, No. 7, 01.08.2005, p. 698-708.

Research output: Contribution to journalArticle

Yeudall, William Andrew ; Miyazaki, Hiroshi ; Ensley, John F. ; Cardinali, Massimo ; Gutkind, J. Silvio ; Patel, Vyomesh. / Uncoupling of epidermal growth factor-dependent proliferation and invasion in a model of squamous carcinoma progression. In: Oral Oncology. 2005 ; Vol. 41, No. 7. pp. 698-708.
@article{6bfc5a5a825941b9b47fcc6a1082156c,
title = "Uncoupling of epidermal growth factor-dependent proliferation and invasion in a model of squamous carcinoma progression",
abstract = "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.",
keywords = "Growth factor, Invasion, Metastasis, Squamous cell carcinoma",
author = "Yeudall, {William Andrew} and Hiroshi Miyazaki and Ensley, {John F.} and Massimo Cardinali and Gutkind, {J. Silvio} and Vyomesh Patel",
year = "2005",
month = "8",
day = "1",
doi = "10.1016/j.oraloncology.2005.03.004",
language = "English (US)",
volume = "41",
pages = "698--708",
journal = "Oral Oncology",
issn = "1368-8375",
publisher = "Elsevier Limited",
number = "7",

}

TY - JOUR

T1 - Uncoupling of epidermal growth factor-dependent proliferation and invasion in a model of squamous carcinoma progression

AU - Yeudall, William Andrew

AU - Miyazaki, Hiroshi

AU - Ensley, John F.

AU - Cardinali, Massimo

AU - Gutkind, J. Silvio

AU - Patel, Vyomesh

PY - 2005/8/1

Y1 - 2005/8/1

N2 - 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.

AB - 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.

KW - Growth factor

KW - Invasion

KW - Metastasis

KW - Squamous cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=22144482067&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22144482067&partnerID=8YFLogxK

U2 - 10.1016/j.oraloncology.2005.03.004

DO - 10.1016/j.oraloncology.2005.03.004

M3 - Article

C2 - 15935723

AN - SCOPUS:22144482067

VL - 41

SP - 698

EP - 708

JO - Oral Oncology

JF - Oral Oncology

SN - 1368-8375

IS - 7

ER -