Colorectal cancer: genetics of development and metastasis

Takayama, Tetsuji; Miyanishi, Koji; Hayashi, Tsuyoshi; Sato, Yasushi; Niitsu, Yoshiro

doi:10.1007/s00535-006-1801-6

Cited by 207 publications

(148 citation statements)

References 84 publications

Supporting

Mentioning

139

Contrasting

Order By: Relevance

“…Metastasis to the liver is the major cause of death in CRC patients (3). The formation of liver metastases is a multistep process involving the escape of tumor cells from a primary CRC, intravasation into the systemic circulation, survival during transit in the vasculature, extravasation into the parenchyma of liver tissues, and ultimately the outgrowth of macroscopic liver metastasis formation through proliferation and angiogenesis (4)(5)(6). Although research has identified multiple genes responsible for liver metastasis (7), the epigenetic alterations that drive metastasis to the liver are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

Zhang

Liu

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

Abstract. MicroRNAs (miRNAs) have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that various miRNAs function as oncogenes or tumor suppressors in colorectal cancer (CRC), the role of miRNAs in mediating liver metastasis remains unexplored. The expression profile of miRNAs in liver metastasis and primary CRC tissues was analyzed by miRNA microarrays and verified by real-time polymerase chain reaction (PCR). In 62 CRC patients, the expression levels of miR-320a were determined by real-time PCR, and the effects on migration and invasion of miR-320a were determined using a transwell assay. miR-320a target genes were confirmed by luciferase assay, real-time PCR and Western blot analysis. A set of miRNAs was found to be dysregulated in the liver metastasis tissues compared to matched primary CRC tissues, and the expression levels of miR-320a were significantly decreased in the liver metastasis tissues examined. miR-320a was correlated with tumor progression in CRC. miR-320a was downregulated in liver metastatic colon cancer cells and inhibited liver metastatic colon cancer cell migration and invasion. miR-320a directly binds to the 3'UTR of neuropilin 1 (NRP-1), a protein that functions as a co-receptor of vascular epithelial growth factor. miR-320a downregulated the expression of NRP-1 at both the mRNA and protein levels. These data demonstrated that miR-320a may be useful for identifying CRC patients that are at an elevated risk for developing liver metastasis. Our findings suggest that miR-320a may be a novel therapeutic candidate for the treatment of colorectal cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

Zhang

Liu

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…There was a clue that TIMP3 may exhibit pro-apoptotic properties in corneal stromal cells. 1 We detected whether Ad-TIMP3 works on colon cancer cells through inducing apoptosis. From Figure 2b, poly ADP-ribose polymerase (PARP) cleavage was increasingly obvious in Ad-TIMP3-treated cells, which indicated that TIMP3 transfer induced apoptosis of CT26 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Many genes have been identified as being involved in migration, adhesion and angiogenesis steps of metastasis process, such as APC, p53 and DCC/SMAD4. 1 Tissue inhibitor of metalloproteinases (TIMPs) are the proteins to anti-act the matrix metalloproteinase (MMP) activity, keeping the balance of TIMPs and MMPs. Among the TIMPs, TIMP3 is demonstrated to be associated with powerful anticancer capacity.…”

Section: Introductionmentioning

confidence: 99%

Tissue inhibitor of metalloproteinases-3 transfer suppresses malignant behaviors of colorectal cancer cells

et al. 2012

View full text Add to dashboard Cite

Colorectal carcinoma is one of the most frequent cancer diseases. For patients with this type of cancer, liver metastases are the main cause of death. Therefore, new therapeutic approaches are urgently needed to improve the outcomes. We found that both mRNA and protein levels of tissue inhibitor of metalloproteinase-3 (TIMP3) were decreased significantly in colorectal cancer tissue when compared with normal mucosa, suggesting that decrease of TIMP3 expression was correlated with malignant behavior of colorectal cancer. We evaluated the power of TIMP3, a new potent multiple functional molecule, as a biotheropeutic tool to treat cancer. Adenovirus-mediated TIMP3 transduction in CT26 colon cancer model demonstrated multiple effects to arrest cancer cell growth and induced massive apoptosis. Also, adenovirally transferred TIMP3 reduced adhesion, migration and invasion behaviors of CT26 cells in vitro. In vivo data showed that TIMP3 suppressed in vivo tumor growth and that liver metastasis was significantly reduced by TIMP3 transduction. This is the first systematic preclinical study to show that TIMP3 may be a potential molecular tool for colon cancer biological therapy.

show abstract

“…FGF1 is a pleiotropic growth factor known to regulate proliferation, migration, and differentiation of target cells, and it has been shown to promote intestinal epithelial cell migration. 17 A recent article has additionally shown that overexpression of FGFR correlates with liver metastasis in CRC, 18 and the splice form IIIc of FGFR3 has been suggested to have oncogenic effect on CRC cells. 19 Because both a block of FGFR and use of a neutralizing FGF1 antibody attenuated cancer cell migration in our assay, we speculate that FGF signaling might be one pathway responsible for the low clinical efficiency seen when using the FAP-inhibitor talabostat on metastatic CRC patients.…”

Section: Discussionmentioning

confidence: 99%

Colorectal Cancer Cells Activate Adjacent Fibroblasts Resulting in FGF1/FGFR3 Signaling and Increased Invasion

Henriksson

Edin

Dahlin

et al. 2011

The American Journal of Pathology

121

100

View full text Add to dashboard Cite

Cancer-associated fibroblasts expressing fibroblast activation protein (FAP) have been implicated in the invasive behavior of colorectal cancer. In this study, we use FAP expression as a marker of fibroblast activation and analyze the effect of activated fibroblasts on colorectal cancer migration and invasion in experimental cell studies. We also investigated the expression pattern of FAP in cancer-associated fibroblasts during transformation from benign to malignant colorectal tumors. In immunohistochemical analyses, FAP was expressed in fibroblasts in all colorectal cancer samples examined, whereas all normal colon, hyperplastic polyps, or adenoma samples were negative. In in vitro studies, conditioned medium from colon cancer cells, but not adenoma cells, activated fibroblasts by inducing FAP expression. These activated fibroblasts increased the migration and invasion of colon cancer cells in Boyden chamber experiments and in a three-dimensional cell culture model. We identify fibroblast growth factor 1/fibroblast growth factor receptor 3 (FGF1/FGFR-3) signaling as mediators leading to the increased migration and invasion. Activated fibroblasts increase their expression of FGF1, and by adding a fibroblast growth factor receptor inhibitor, as well as an FGF1-neutralizing antibody, we reduced the migration of colon cancer cells. Our findings provide evidence of a possible molecular mechanism involved in the cross talk between cancer cells and fibroblasts leading to cancer cell invasion.

show abstract

Colorectal cancer: genetics of development and metastasis

Cited by 207 publications

References 84 publications

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

Tissue inhibitor of metalloproteinases-3 transfer suppresses malignant behaviors of colorectal cancer cells

Colorectal Cancer Cells Activate Adjacent Fibroblasts Resulting in FGF1/FGFR3 Signaling and Increased Invasion

Contact Info

Product

Resources

About