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- W2012247075 abstract "We have previously shown that pancreatic stellate cells (PSCs) i) produce the desmoplastic reaction in pancreatic cancer (PC), ii) facilitate local tumour growth, and iii) stimulate proliferation while inhibiting apoptosis of PC cells. However, the role of PSCs in tumour angiogenesis and distant metastasis has not been fully elucidated. Aims: Using an orthotopic model of PC, to determine i) whether the presence of PSCs increases tumour angiogenesis and ii) whether PSCs accompany tumour cells to metastatic sites. Method: Female athymic mice were injected into the pancreas as follows: i) Angiogenesis study (n = 7 pairs) - suspension of MiaPaCa2 cells (PC cell line) ± human PSCs (1 × 106 cells each). Mice were killed 7 weeks later and tumours assessed by immmunostaining and morphometry for the endothelial cell marker CD31; ii) Metastasis study (n = 3 pairs) - suspension of AsPC1 cells (female PC cell line) ± male human PSCs (1 × 106 cells each). Metastatic nodules were stained by fluorescent in situ hybridization (FISH) for the 'y' chromosome. Results: i) Angiogenesis study - Tumours in mice receiving MiaPaCa2+hPSCs exhibited significantly increased CD31 staining compared to those injected with MiaPaCa2 alone [grid point counting scores per high power field 7.2 ± 0.8 vs 3.5 ± 1.0; p < 0.005]. ii) Metastasis study - Mice injected with AsPC1 + hPSCs exhibited larger tumours and increased rates of metastasis compared to mice injected with AsPC1 alone confirming our previously published results with other PC cell lines. Positive FISH staining for the 'y' chromosome was evident in metastatic nodules in the mediastinum, diaphragm and liver hilum in mice injected with AsPC1 + male hPSCs. Conclusions: In the presence of PSCs, angiogenesis in pancreatic tumours is significantly increased. Notably, our results indicate that PSCs accompany cancer cells to metastatic sites. Implication: PSCs promote tumor progression by not only facilitating cancer cell survival but also by stimulating neo-angiogenesis. Moreover, PSCs travel to distant metastatic sites with PC cells raising the possibility that PSCs facilitate seeding, survival and growth of cancer cells at metastatic sites." @default.
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- W2012247075 date "2008-11-01" @default.
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- W2012247075 title "PANCREATIC STELLATE CELLS STIMULATE ANGIOGENESIS IN PANCREATIC CANCER AND ACCOMPANY PANCREATIC CANCER CELLS TO DISTANT METASTATIC SITES" @default.
- W2012247075 doi "https://doi.org/10.1097/01.mpa.0000335420.28357.d3" @default.
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