Macrophage-stimulating Protein and Its Receptor in Non-small-cell Lung Tumors: Induction of Receptor Tyrosine Phosphorylation and Cell Migration
العنوان: | Macrophage-stimulating Protein and Its Receptor in Non-small-cell Lung Tumors: Induction of Receptor Tyrosine Phosphorylation and Cell Migration |
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المؤلفون: | Rodica L. Emanuel, Sherry A. Graham, Viji Shridhar, David I. Smith, David J. Sugarbaker, Ming Hai Wang, Mary E. Sunday, Christopher G. Willett |
المصدر: | American Journal of Respiratory Cell and Molecular Biology. 18:489-496 |
بيانات النشر: | American Thoracic Society, 1998. |
سنة النشر: | 1998 |
مصطلحات موضوعية: | Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Lung Neoplasms, Clinical Biochemistry, Gene Expression, Receptors, Cell Surface, Biology, Lung injury, Receptor tyrosine kinase, chemistry.chemical_compound, Paracrine signalling, Cell Movement, Carcinoma, Non-Small-Cell Lung, Proto-Oncogene Proteins, parasitic diseases, Tumor Cells, Cultured, medicine, Humans, RNA, Messenger, Phosphorylation, Protein Precursors, Growth Substances, Lung cancer, Autocrine signalling, Molecular Biology, Hepatocyte Growth Factor, MST1R, Receptor Protein-Tyrosine Kinases, Tyrosine phosphorylation, Cell Biology, medicine.disease, Primary tumor, chemistry, Enzyme Induction, biology.protein, Cancer research |
الوصف: | 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. |
تدمد: | 1535-4989 1044-1549 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6b9bd20b5698fbebbb316fc4bcfb67a1Test https://doi.org/10.1165/ajrcmb.18.4.2978Test |
رقم الانضمام: | edsair.doi.dedup.....6b9bd20b5698fbebbb316fc4bcfb67a1 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15354989 10441549 |
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