Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung: Possible implications for neuroendocrine cell survival

Christopher G. Willett, David I. Smith, Viji Shridhar, Ming Hai Wang, Rodica L. Emanuel, Kirit Patidar, Sherry A. Graham, Fan Zhang, Victoria Hatch, David J. Sugarbaker, Mary E. Sunday

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33 Scopus citations


Transient pulmonary neuroendocrine cell hyperplasia and non- neuroendocrine lung tumors develop in nitrosamine-treated hamsters, which we hypothesized might modulate epithelial cell phenotype by expressing gene(s) homologous to human chromosome 3p gene(s) deleted in small cell carcinoma of the lung (SCLC). We differentially screened a chromosome 3 library using nitrosamine-treated versus normal hamster lung cDNAs and identified hepatocyte growth factor-like/macrophage-stimulating protein (HGFL/MSP) in injured lung. HGFL/MSP mRNA is low to undetectable in human SCLC and carcinoid tumors, but the HGFL/MSP tyrosine kinase receptor, RON, is present and functional on many of these neuroendocrine tumors. In H835, a pulmonary carcinoid cell line, and H 187, a SCLC cell line, HGFL/MSP induced adhesion/flattening and apoptosis. Using viable cell counts to assess proliferation after 14 d of treatment with HGFL/MSP, there is growth inhibition of H835 but not H187. Nitrosamine-treated hamsters also demonstrate pulmonary neuroendocrine cell apoptosis in situ during the same time period as expression of the endogenous HGFL/MSP gene, immediately preceding the spontaneous regression of neuroendocrine cell hyperplasia. These observations suggest that HGFL/MSP might regulate neuroendocrine cell survival during preneoplastic lung injury, which could influence the ultimate tumor cell phenotype.

Original languageEnglish (US)
Pages (from-to)2979-2991
Number of pages13
JournalJournal of Clinical Investigation
Issue number12
StatePublished - Jun 15 1997



  • Apoptosis
  • Cell adhesion
  • Cell proliferation
  • Nitrosamines
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Medicine(all)

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