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Stromal Reaction (stromal + reaction)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

In vivo and in vitro Interactions between Human Colon Carcinoma Cells and Hepatic Stellate Cells

CANCER SCIENCE, Issue 12 2000
Sadatoshi Shimizu
Stromal reaction is important for the growth of cancer both in primary and metastatic sites. To demonstrate this reaction during the hepatic metastasis of human colon carcinoma, we histologically investigated alterations to the distribution and phenotype of hepatic stellate cells (HSCs), the only mesenchymal cells in the liver parenchyma, using a nude mouse model. Intrasplenically injected colon carcinoma LM-H3 cells migrated into the space of Disse and underwent proliferation, in close association with hepatocytes and HSCs, at 2 days. At 14 days, HSCs were accumulated around the tumor mass and expressed ,-smooth muscle actin, a marker for HSC activation. We next investigated in vitro the growth factors involved in the interactions between LM-H3 cells and HSCs. Conditioned medium of rat HSCs which underwent culture-induced activation contained platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor (HGF) and transforming growth factor (TGF),, and could augment LM-H3-cell proliferation and migration. Neutralizing antibodies against PDGF-AA and PDGF-BB and those against PDGF-BB and HGF inhibited proliferation and migration, respectively, of LM-H3 cells, whereas antibody against TGF-, had no effect. LM-H3 cells expressed PDGF receptors-, and -, and c-met. Conditioned medium of LM-H3 cells contained PDGF-AB, and could enhance HSC proliferation and migration. This augmenting effect was suppressed by treatment with anti-PDGF-AB antibody. The present study has demonstrated that bidirectional interactions involving PDGF and HGF take place in vitro between colon carcinoma cells and HSCs, raising the possibility that similar interactions might be involved in the stromal reaction during hepatic metastasis. [source]

Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow-derived endothelial cells and myofibroblasts in cancer-induced stroma

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2005
Takafumi Sangai
Abstract Cancer-stromal interaction is well known to play important roles during cancer progression. Recently we have demonstrated that bone marrow-derived vascular endothelial cells (BMD-VE) and myofibroblasts (BMD-MF) are recruited into the human pancreatic cancer cell line Capan-1 induced stroma. To assess the effect of the difference in cancer cell types on the recruitment of BMD-VE and BMD-MF, 10 kinds of human cancer cell line were implanted into the subctaneous tissue of the immunodeficient mice transplanted with bone marrow of double-mutant mice (RAG-1,/, ,-gal Tg or RAG-1,/, GFP Tg). The recruitment frequency of BMD-VE (%BMD-VE) and BMD-MF (%BMD-MF), and tumor-associated parameters [tumor volume (TV), microvessel density (MVD) and stromal proportion (%St)] were measured. The correlation among them was analyzed. Although %BMD-VE and %BMD-MF varied (from 0 to 21.6%, 0 to 29.6%, respectively), depending on the cancer cell line, both parameters were significantly correlated with %St (p < 0.005). Furthermore %BMD-VE and %BMD-MF also significantly correlated (p < 0.005). In order to assess the effect of tumor growth sites on the recruitment of the cells of interest, a human pancreatic cancer cell line, Capan-1, was transplanted into 5 different sites: subcutaneous tissue, peritoneum, liver, spleen and lung. Tumors in the subcutaneous tissue and peritoneum induced desmoplastic stroma (%St = 22.7%, 19.5%, respectively) and contained BMD-VE (%BMD-VE = 21.6%, 16.5% respectively) and BMD-MF (%BMD-MF = 29.6%, 24.5%, respectively), but weak stromal induction without recruitment of BMD-VE or -MF was observed in the tumors at of the liver, spleen and lung (%St = 9.7%, 9.1%, 5.4%, respectively). cDNA microarray analysis identified the 29 genes that expression was especially up- or down-regulated in the cell line that induced an abundant stromal reaction. However they did not encoded the molecules that were directly involved in stromal cell recruitment (chemokines), differentiation (cytokines) or proliferation (growth factors). These results indicate that the recruitment of BMD-VE and -MF is required for stromal formation during cancer progression and that the cancer microenvironment is important in stromal reaction and the recruitment of BMD-VE and -MF. © 2005 Wiley-Liss, Inc. [source]