Macrophage-stimulating protein and its receptor in non-small-cell lung tumors: Induction of receptor tyrosine phosphorylation and cell migration

Christopher G. Willett, Ming Hai Wang, Rodica L. Emanuel, Sherry A. Graham, David I Smith, Vijayalakshmi Shridhar, David J. Sugarbaker, Mary E. Sunday

Research output: Contribution to journalArticle

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Abstract

Previously, we identified macrophage-stimulating protein (MSP) as being expressed during hamster lung injury induced by nitrosamine carcinogens. Transient, generalized epithelial-cell hyperplasia during the preneoplastic period, and eventually nonneuroendocrine (non-NE) lung tumors, are known to develop in these nitrosamine-treated hamsters. We wished to test the hypothesis that MSP and its tyrosine kinase receptor, RON, might represent an autocrine/paracrine system involved in the pathogenesis of human nonneuroendocrine lung tumors, the non-small-cell carcinomas (NSCLCs). We found that this occurred in a paracrine fashion in three of eight primary human NSCLCs that expressed messenger RNA (mRNA) for MSP at high levels in histologically normal lung adjacent to the tumor, but not in the primary tumor, together with mRNA for RON in both normal and tumor tissue. MSP and RON could also constitute an autocrine/paracrine system in human NSCLC cell lines: five of 16 cell lines (squamous and adenosquamous) expressed both MSP and RON; and an additional five of 16 cell lines expressed RON without detectable MSP. Although three cases of primary squamous-cell carcinomas expressed MSP (two of three in the tumor and one of three in nonneoplastic lung), mRNA for RON was not detectable in these cases. RON was functional in all tested RON mRNA-positive cell lines, with exogenous MSP inducing RON-mediated tyrosine phosphorylation. Treatment of a RON-positive adenosquamous carcinoma cell line with MSP additionally resulted in increased motility in a cell-migration assay, suggesting that MSP might promote cell migration of some NSCLCs. In conclusion, MSP and RON might represent an autocrine/paracrine system involved in the pathogenesis of lung cancer, although the nature of the biologic responses in different cell types might vary considerably.

Original languageEnglish (US)
Pages (from-to)489-496
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume18
Issue number4
StatePublished - 1998

Fingerprint

Phosphorylation
Cell Movement
Tumors
Cells
Lung
Neoplasms
Cell Line
Nitrosamines
Messenger RNA
Carcinoma
Cricetinae
tyrosine receptor
macrophage stimulating protein
rice bran saccharide
RON protein
Cell Migration Assays
Adenosquamous Carcinoma
Receptor Protein-Tyrosine Kinases
Lung Injury
Non-Small Cell Lung Carcinoma

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

Macrophage-stimulating protein and its receptor in non-small-cell lung tumors : Induction of receptor tyrosine phosphorylation and cell migration. / Willett, Christopher G.; Wang, Ming Hai; Emanuel, Rodica L.; Graham, Sherry A.; Smith, David I; Shridhar, Vijayalakshmi; Sugarbaker, David J.; Sunday, Mary E.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 18, No. 4, 1998, p. 489-496.

Research output: Contribution to journalArticle

Willett, Christopher G. ; Wang, Ming Hai ; Emanuel, Rodica L. ; Graham, Sherry A. ; Smith, David I ; Shridhar, Vijayalakshmi ; Sugarbaker, David J. ; Sunday, Mary E. / Macrophage-stimulating protein and its receptor in non-small-cell lung tumors : Induction of receptor tyrosine phosphorylation and cell migration. In: American Journal of Respiratory Cell and Molecular Biology. 1998 ; Vol. 18, No. 4. pp. 489-496.
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AU - Emanuel, Rodica L.

AU - Graham, Sherry A.

AU - Smith, David I

AU - Shridhar, Vijayalakshmi

AU - Sugarbaker, David J.

AU - Sunday, Mary E.

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