RRC ID 67387
Author Sugimoto T, Takiguchi Y, Kurosu K, Kasahara Y, Tanabe N, Tatsumi K, Hiroshima K, Minamihisamatsu M, Miyamoto T, Kuriyama T.
Title Growth factor-mediated interaction between tumor cells and stromal fibroblasts in an experimental model of human small-cell lung cancer.
Journal Oncol Rep
Abstract Malignant tumors induce development of their own stromal tissues during the processes of growth, progression and metastasis. Since the vascular architecture among the various stromal elements is well known to facilitate tumor growth and has been a target of therapy, the importance of stromal fibroblasts has recently been established. To elucidate the interaction between the tumor and its stromal fibroblasts, the present study took advantage of a unique experimental model consisting of a human small-cell lung cancer cell line, WA-ht, and its mouse stromal fibroblast cell line, WA-mFib, both originally derived from a xenograft tumor in a mouse subcutis. Co-culture with the WA-mFib cells significantly augmented the plating efficiency of WA-hT cells in vitro, and their co-inoculation in nude mice shortened latency and tumor doubling time. Histochemical detection of beta-gal, transfected into WA-mFib cells, demonstrated their contribution to the nude mouse xenograft tumor formation as its tumor stroma. Elevated hepatocyte growth factor (HGF) from fibroblasts followed by elevated production of vascular endothelial growth factor (VEGF) from both tumor cells and fibroblasts were demonstrated by ELISA in supernatants of their co-culture, accompanied by enhanced colonogenicity of the tumor cells; these enhanced features were not observed in their respective monocultures. Antisense oligonucleotides to HGF cancelled these augmentation effects with co-culture. The findings highlight the substantial roles of tumor stromal fibroblasts, interacting with soluble growth factors, in promoting the malignant propensity of the tumor.
Volume 14(4)
Pages 823-30
Published 2005-10-1
PMID 16142338
MeSH Animals Biopsy Carcinoma, Small Cell / metabolism* Cell Line, Tumor Coculture Techniques Culture Disease Models, Animal Enzyme-Linked Immunosorbent Assay Female Fibroblasts / cytology* Fibroblasts / metabolism* Growth Substances / metabolism* Hepatocyte Growth Factor / metabolism* Humans Lac Operon Lung Neoplasms / metabolism* Male Mice Mice, Inbred BALB C Mice, Nude Middle Aged Neoplasm Metastasis Oligonucleotides / chemistry Oligonucleotides, Antisense / chemistry Oligonucleotides, Antisense / pharmacology Stromal Cells / cytology* Stromal Cells / metabolism Time Factors Transfection Vascular Endothelial Growth Factor A / metabolism beta-Galactosidase / metabolism
IF 3.417
Human and Animal Cells BALB/3T3 clone A31(RCB0005)