In vitro inhibition of matriptase prevents invasive growth of cell lines of prostate and colon carcinoma

Förbs, Diana; Thiel, Stefan; Stella, Maria Cristina; Stürzebecher, Anne; Schweinitz, Andrea; Steinmetzer, Torsten; Stürzebecher, Jörg; Uhland, Kerstin

doi:10.3892/ijo.27.4.1061

Cited by 52 publications

(68 citation statements)

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“…It is intriguing to consider that TMPRSS4 may modulate the activation of MAPKs to contribute to a malignant phenotype of cancer cells. Our study appears to provide the first evidence that a TTSP family member is positively involved in cancer cell proliferation in vitro; others have reported that inhibition of matriptase/MT-SP1 or TMPRSS1/ hepsin does not affect cell proliferation in vitro, although cell invasion is impaired (Galkin et al, 2004;Suzuki et al, 2004;Forbs et al, 2005;Xuan et al, 2006). However, in contrast to the reduced cell proliferation observed following knockdown of TMPRSS4 in NCI-H322 cells, TMPRSS4 overexpression does not appear to confer a growth advantage to colon cancer SW480 cells in vitro.…”

Section: Discussionmentioning

confidence: 54%

TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial–mesenchymal transition

et al. 2007

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TMPRSS4 is a novel type II transmembrane serine protease found at the cell surface that is highly expressed in pancreatic, colon and gastric cancer tissues. However, the biological functions of TMPRSS4 in cancer are unknown. Here we show, using reverse transcription-PCR, that TMPRSS4 is highly elevated in lung cancer tissues compared with normal tissues and is also broadly expressed in a variety of human cancer cell lines. Knockdown of TMPRSS4 by small interfering RNA treatment in lung and colon cancer cell lines was associated with reduction of cell invasion and cell-matrix adhesion as well as modulation of cell proliferation. Conversely, the invasiveness, motility and adhesiveness of SW480 colon carcinoma cells were significantly enhanced by TMPRSS4 overexpression. Furthermore, overexpression of TMPRSS4 induced loss of E-cadherin-mediated cell-cell adhesion, concomitant with the induction of SIP1/ZEB2, an Ecadherin transcriptional repressor, and led to epithelialmesenchymal transition events, including morphological changes, actin reorganization and upregulation of mesenchymal markers. TMPRSS4-overexpressing cells also displayed markedly increased metastasis to the liver in nude mice upon intrasplenic injection. Taken together, these studies suggest that TMPRSS4 controls the invasive and metastatic potential of human cancer cells by facilitating an epithelial-mesenchymal transition; TMPRSS4 may be a potential therapeutic target for cancer treatment.

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Section: Discussionmentioning

confidence: 54%

TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial–mesenchymal transition

et al. 2007

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“…Inhibition of endogenous matriptase synthesis or treatment of cells with matriptase inhibitors has been shown to reduce invasion of prostate carcinoma cells, suggesting that matriptase plays a role in the properties of the invasive phenotype (Forbs et al 2005, Sanders et al 2006, Tsui et al 2008a. In this study, we found that overexpression of GDF15 resulted in increased matriptase expression in vitro, which may account for the increasing invasiveness of PC-3 cells with forced overexpression of GDF15.…”

Section: Discussionmentioning

confidence: 99%

Growth differentiation factor-15 upregulates interleukin-6 to promote tumorigenesis of prostate carcinoma PC-3 cells

Tsui¹,

Chang²,

Feng³

et al. 2012

Journal of Molecular Endocrinology

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Growth differentiation factor-15 (GDF15), a member of the transforming growth factor-b superfamily, is associated with human cancer progress. We evaluated the role GDF15 plays in tumorigenesis of prostate carcinoma PC-3 cells. Results from real-time RT-PCR and ELISA revealed that expression of GDF15 was approximately threefold higher in LNCaP cells than in PC-3 cells. Other prostate cell lines (PZ-HPV-7, CA-HPV-10, and DU145 cells) expressed extremely low levels of GDF15. Stable overexpression of GDF15 in PC-3 cells enhanced the degree of cell proliferation and invasion as shown in the 3 H-thymidine incorporation assay and in the Matrigel invasion assay respectively. Soft agar assays and xenograft animal studies indicated that overexpression of GDF15 in PC-3 cells increased tumorigenesis in vitro and in vivo. Results from RT-PCR, immunoblot, and reporter assays revealed that overexpression of GDF15 resulted in decreased expression of maspin and upregulation of interleukin-6 (IL6), matriptase, and N-myc downstream-regulated gene 1 (NDRG1) expression. Further studies revealed that overexpression of IL6 enhanced GDF15 expression in LNCaP cells while knockdown of IL6 blocked the expression of GDF15 in PC-3 cells, suggesting that expression of GDF15 is upregulated by IL6. This study demonstrated that expression of GDF15 induces cell proliferation, invasion, and tumorigenesis of prostate carcinoma PC-3 cells. The enhancement of tumorigenesis and invasiveness of prostate carcinoma cells that stably overexpress GDF15 may be caused by the dysregulation of maspin, matriptase, and IL6 gene expression. The expression of GDF15 and IL6 is controlled via a positive feedback loop in PC-3 cells.

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“…Matriptase activity has been associated with cell proliferation via activation of growth factors in some cellular contexts (12), raising the possibility that the impaired ability to develop TEER in matriptase-silenced Caco-2 monolayers could be due to reduced cell proliferation. Cell proliferation assays revealed that there were similar cell numbers in matriptasesilenced and control Caco-2 monolayers (Fig.…”

Section: Caco-2 Cell Proliferation In Polarized Monolayers Is Unaffecmentioning

confidence: 99%

Membrane-anchored serine protease matriptase regulates epithelial barrier formation and permeability in the intestine

Buzza

Netzel‐Arnett

Shea‐Donohue³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

156

192

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The intestinal epithelium serves as a major protective barrier between the mammalian host and the external environment. Here we show that the transmembrane serine protease matriptase plays a pivotol role in the formation and integrity of the intestinal epithelial barrier. St14 hypomorphic mice, which have a 100-fold reduction in intestinal matriptase mRNA levels, display a 35% reduction in intestinal transepithelial electrical resistance (TEER). Matriptase is expressed during intestinal epithelial differentiation and colocalizes with E-cadherin to apical junctional complexes (AJC) in differentiated polarized Caco-2 monolayers. Inhibition of matriptase activity using a specific peptide inhibitor or by knockdown of matriptase by siRNA disrupts the development of TEER in barrierforming Caco-2 monolayers and increases paracellular permeability to macromolecular FITC-dextran. Loss of matriptase was associated with enhanced expression and incorporation of the permeabilityassociated, "leaky" tight junction protein claudin-2 at intercellular junctions. Knockdown of claudin-2 enhanced the development of TEER in matriptase-silenced Caco-2 monolayers, suggesting that the reduced barrier integrity was caused, at least in part, by an inability to regulate claudin-2 expression and incorporation into junctions. We find that matriptase enhances the rate of claudin-2 protein turnover, and that this is mediated indirectly through an atypical PKCζ-dependent signaling pathway. These results support a key role for matriptase in regulating intestinal epithelial barrier competence, and suggest an intriguing link between pericellular serine protease activity and tight junction assembly in polarized epithelia.claudin-2 | intestinal barrier | St14 | type II transmembrane serine protease | tight junction

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In vitro inhibition of matriptase prevents invasive growth of cell lines of prostate and colon carcinoma

Cited by 52 publications

References 0 publications

TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial–mesenchymal transition

TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial–mesenchymal transition

Growth differentiation factor-15 upregulates interleukin-6 to promote tumorigenesis of prostate carcinoma PC-3 cells

Membrane-anchored serine protease matriptase regulates epithelial barrier formation and permeability in the intestine

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