Invasion and metastasis are the deadly face of malignant tumors. Considering the high rate of incidence and mortality of colorectal cancer, it is critical to determine the mechanisms of its dissemination. In the paral...Invasion and metastasis are the deadly face of malignant tumors. Considering the high rate of incidence and mortality of colorectal cancer, it is critical to determine the mechanisms of its dissemination. In the parallel investigation of the invasive front and tumor center area of colorectal cancer (CRC), observation of heterogeneous β-catenin distribution and epithelial-mesenchymal transition (EMT) at the invasive front suggested that there might be a crosstalk between tumor cells and the tumor microenvironment. Wnt signaling pathway is also involved in the cancer progression due to its key role in CRC tumorigenesis. Moreover, in recent years, there is increasing evidence that the regulators of microenvironment, including extracellular matrix, growth factors and inflammatory factors, are associated with the activation of Wnt pathway and the mobility of tumor cells. In this review, we will try to explain how these molecules trigger metastasis via the Wnt pathway.展开更多
AIM： To investigate the expression of B7-H1 in human colorectal carcinoma （CRC） to define its regulating ef- fects on T cells in tumor microenvironment.
Colorectal cancer(CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by ...Colorectal cancer(CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by tumour microenvironment(TME). The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis. Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors(angiogenic/inflammatory/immune) which contribute to cancer cell proliferation, invasion, neoangiogenesis, evasion of immune surveillance and therapy resistance. Furthermore, adipocytes represent a fuel rich source for increasing energy demand of rapidly proliferating tumour cells. Interestingly, a relationship between obesity and molecular variants in CRC has recently been identified. Whether adipose tissue promotes cancer progression in subsets of molecular phenotypes or whether local tissue adipocytes are involved in inactivation of tumour suppressor genes and/or activation of oncogenes still needs to be explored. This editorial highlights the major findings related to crosstalk between adipocytes and colon cancer cells and how local paracrine interactions may promote cancer progression. Furthermore, we provide future strategies in studying colonic TME which could provide insights in bidirectional cross-talk mechanisms between adipocytes and colonic epithelial cells. This could enable to decipher critical signalling pathways of both early colonic carcinogenesis and cancer progression.展开更多
Objective： Cancer-associated fibroblasts （CAFs） are one of the hallmarks of the cancer microenvironment. Recent evidence has indicated that CAFs are more competent in enhancing cancer cell growth and migration than...Objective： Cancer-associated fibroblasts （CAFs） are one of the hallmarks of the cancer microenvironment. Recent evidence has indicated that CAFs are more competent in enhancing cancer cell growth and migration than normal fibroblasts. However, the unique protein expression of CAFs has not been fully elucidated. This study aims to investigate the characterizations of colon CAFs by comparing the differential protein expression between CAFs and normal fibroblasts. Methods： Primary fibroblasts were isolated from surgical specimen of human colon cancer and matched normal colonic tissue. Purity of the cell population was verified through immunostain analysis. Total cell lysates and conditioned media from each group of cells were extracted, and protein expression analysis was con- ducted using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF-MS） ProteinChip platform. Results： Most primary cells showed typical fibroblast-like features after two weeks. Increased proportion of a-smooth muscle actin-positive myofibroblasts was detected within the CAFs in four of the six pairs of primary cells. Fibroblast activation protein was weakly expressed in most cells without differences. Using SELDI-TOF-MS ProteinChip platform, four protein peaks mass over charge ratio （m/z） 1142, 3011, 4035, and 4945 were detected in the total cell lysates, and two protein peaks m/z 1368 and 1389 were detected in the conditioned media. The potential candidate proteins found in the Swiss-Prot database include morphogenetic neuropeptides, FMRFamide-related peptides, insulin-like growth factor II, thymosin 13-4-like protein 3, and tight junction-associated protein 1. Conclusions： Using the SELDI-ProteinChip platform, differential protein expressions were identified in colon CAFs compared with normal colonic stromal fibroblasts. The complex proteomic alternations in colon CAFs may play important roles related to the colon cancer microenvironment.展开更多
基金Supported by The Science and Technology Development Foundation of Shanghai, No. 064119512
文摘Invasion and metastasis are the deadly face of malignant tumors. Considering the high rate of incidence and mortality of colorectal cancer, it is critical to determine the mechanisms of its dissemination. In the parallel investigation of the invasive front and tumor center area of colorectal cancer (CRC), observation of heterogeneous β-catenin distribution and epithelial-mesenchymal transition (EMT) at the invasive front suggested that there might be a crosstalk between tumor cells and the tumor microenvironment. Wnt signaling pathway is also involved in the cancer progression due to its key role in CRC tumorigenesis. Moreover, in recent years, there is increasing evidence that the regulators of microenvironment, including extracellular matrix, growth factors and inflammatory factors, are associated with the activation of Wnt pathway and the mobility of tumor cells. In this review, we will try to explain how these molecules trigger metastasis via the Wnt pathway.
基金Supported by Grants from the Major State Basic Research Development Program of China 973 Program,No.2007CB512402National Natural Science Foundation of China,No.31100634+1 种基金Natural Science Foundation of Jiangsu Province,No.BK2010161"333" Project of Wuxi City,Jiangsu Province,No.CAE00901-09
文摘AIM： To investigate the expression of B7-H1 in human colorectal carcinoma （CRC） to define its regulating ef- fects on T cells in tumor microenvironment.
文摘Colorectal cancer(CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by tumour microenvironment(TME). The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis. Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors(angiogenic/inflammatory/immune) which contribute to cancer cell proliferation, invasion, neoangiogenesis, evasion of immune surveillance and therapy resistance. Furthermore, adipocytes represent a fuel rich source for increasing energy demand of rapidly proliferating tumour cells. Interestingly, a relationship between obesity and molecular variants in CRC has recently been identified. Whether adipose tissue promotes cancer progression in subsets of molecular phenotypes or whether local tissue adipocytes are involved in inactivation of tumour suppressor genes and/or activation of oncogenes still needs to be explored. This editorial highlights the major findings related to crosstalk between adipocytes and colon cancer cells and how local paracrine interactions may promote cancer progression. Furthermore, we provide future strategies in studying colonic TME which could provide insights in bidirectional cross-talk mechanisms between adipocytes and colonic epithelial cells. This could enable to decipher critical signalling pathways of both early colonic carcinogenesis and cancer progression.
基金supported by the National Natural Science Foundation of China (Nos. 81000892, 81071801, and 30801341)the Research Fund for the Doctoral Program of Higher Education of China (No. 200803351107)
文摘Objective： Cancer-associated fibroblasts （CAFs） are one of the hallmarks of the cancer microenvironment. Recent evidence has indicated that CAFs are more competent in enhancing cancer cell growth and migration than normal fibroblasts. However, the unique protein expression of CAFs has not been fully elucidated. This study aims to investigate the characterizations of colon CAFs by comparing the differential protein expression between CAFs and normal fibroblasts. Methods： Primary fibroblasts were isolated from surgical specimen of human colon cancer and matched normal colonic tissue. Purity of the cell population was verified through immunostain analysis. Total cell lysates and conditioned media from each group of cells were extracted, and protein expression analysis was con- ducted using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF-MS） ProteinChip platform. Results： Most primary cells showed typical fibroblast-like features after two weeks. Increased proportion of a-smooth muscle actin-positive myofibroblasts was detected within the CAFs in four of the six pairs of primary cells. Fibroblast activation protein was weakly expressed in most cells without differences. Using SELDI-TOF-MS ProteinChip platform, four protein peaks mass over charge ratio （m/z） 1142, 3011, 4035, and 4945 were detected in the total cell lysates, and two protein peaks m/z 1368 and 1389 were detected in the conditioned media. The potential candidate proteins found in the Swiss-Prot database include morphogenetic neuropeptides, FMRFamide-related peptides, insulin-like growth factor II, thymosin 13-4-like protein 3, and tight junction-associated protein 1. Conclusions： Using the SELDI-ProteinChip platform, differential protein expressions were identified in colon CAFs compared with normal colonic stromal fibroblasts. The complex proteomic alternations in colon CAFs may play important roles related to the colon cancer microenvironment.
