‘Increased expression of seprase, a membrane-type serine protease, is associated with lymph node metastasis in human colorectal cancer’

Iwasa, Satoshi; Okada, Kyoko; Chen, Wen-Tien; Jin, Xin; Yamane, Tetsu; Ooi, Akishi; Mitsumata, Masako

doi:10.1016/j.canlet.2004.06.030

Cited by 75 publications

(58 citation statements)

References 29 publications

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“…Many studies have reported that FAP-α expression in stromal tissue is correlated with tumor invasion and metastasis in colorectal cancer based on immunohistochemical analysis (26,27). Our results also suggest that FAP-α expression can be used to predict poor prognosis in rectal cancer patients who have undergone pre-operative CRT.…”

Section: Discussionsupporting

confidence: 62%

Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy

Saigusa

Toiyama²,

Yokoe³

et al. 2011

Int J Oncol

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Abstract. Cancer-associated fibroblasts (CAFs) in the stroma play an important role in influencing the proliferation, invasion and metastasis of cancer cells. Fibroblast activation protein-α (FAP-α) is known as a marker of CAFs, while stromal cell-derived factor-1 (SDF-1) is primarily expressed by CAFs. Herein, we investigated whether the expression levels of these genes are associated with clinical outcome after pre-operative chemoradiotherapy (CRT) in rectal cancer patients. We obtained total RNA from residual cancer stroma using microdissection from a total of 52 rectal cancer specimens from patients who underwent pre-operative CRT, we performed transcriptional analyses, and the serum protein concentrations in 40 matched microdissected specimens were measured by enzyme-linked immunosorbent assay. Additionally, we sought to clarify the location of FAP-α and SDF-1 expression using immunohistochemical staining. Of the 52 patients, 15.6 and 36.8% showed detectable FAP-α and SDF-1 mRNA expression, respectively. A significant correlation was observed between stromal FAP-α and SDF-1 mRNA levels. Moreover, there was a significant correlation between stromal SDF-1 gene expression levels and serum protein levels. Patients who developed distant recurrences after CRT had positive expression of both genes (P<0.05). The positive expression of both genes was also associated with poor probability of recurrence-free and overall survival (P<0.05). Patients with elevated serum SDF-1 levels had equally poor overall survival as those with positive stromal SDF-1 gene expression (P<0.05). In immunohistochemistry, both FAP-α and SDF-1 expression was observed in certain activated fibroblasts. In conclusion, FAP-α and SDF-1 expression was shown to be involved in tumor re-growth and recurrence in rectal cancer patients treated with pre-operative CRT.

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Section: Discussionsupporting

confidence: 62%

Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy

Saigusa

Toiyama²,

Yokoe³

et al. 2011

Int J Oncol

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“…High levels of FAP immunoreactivity have been positively correlated with the invasive behavior of several malignant tumors, and abundant expression has been associated with lymph node metastasis in CRC. 16 Most previous studies have focused on FAP protease activity, which degrades extracellular matrix molecules, thereby creating a milieu more conductive to invasion as the cause of increased invasion. However, FAP is a membrane-bound protease and should not be present in the conditioned medium from activated fibroblasts.…”

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

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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.

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“…In addition, seprase associates with uPAR and dipeptidyl peptidase IV regulating invasion and migration of fibroblast cells (Ghersi et al, 2002). Seprase activity is also associated with increased metastasis in vivo (Iwasa et al, 2003). Hepsin is a type II transmembrane serine protease normally expressed in hepatocytes (Leytus et al, 1988).…”

Section: Other Proteases In Cell Migration and Invasionmentioning

confidence: 99%

Gelatinase-mediated migration and invasion of cancer cells

Björklund

Koivunen

2005

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

463

609

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‘Increased expression of seprase, a membrane-type serine protease, is associated with lymph node metastasis in human colorectal cancer’

Cited by 75 publications

References 29 publications

Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy

Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy

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

Gelatinase-mediated migration and invasion of cancer cells

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