Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow‐derived endothelial cells and myofibroblasts in cancer‐induced stroma
Open Access
- 23 February 2005
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 115 (6), 885-892
- https://doi.org/10.1002/ijc.20969
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−/− β‐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.Keywords
This publication has 36 references indexed in Scilit:
- Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1–Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor CellsCirculation Research, 2003
- Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiationJournal of Leukocyte Biology, 2003
- Molecular basis of angiogenesis and cancerOncogene, 2003
- Multiple Organ Engraftment by Bone‐Marrow‐Derived Myofibroblasts and Fibroblasts in Bone‐Marrow‐Transplanted MiceThe International Journal of Cell Cloning, 2003
- Bone marrow-derived, endothelial progenitor-like cells as angiogenesis-selective gene-targeting vectorsGene Therapy, 2003
- Peripheral Blood “Endothelial Progenitor Cells” Are Derived From Monocyte/Macrophages and Secrete Angiogenic Growth FactorsCirculation, 2003
- CD34−Blood‐Derived Human Endothelial Cell ProgenitorsThe International Journal of Cell Cloning, 2001
- The Hallmarks of CancerCell, 2000
- PDGF-A Signaling Is a Critical Event in Lung Alveolar Myofibroblast Development and AlveogenesisCell, 1996
- Microvessel count predicts metastatic disease and survival in non‐small cell lung cancerThe Journal of Pathology, 1995