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MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer.

Naito Y, Sakamoto N, Oue N, Yashiro M, Sentani K, Yanagihara K, Hirakawa K, Yasui W - Cancer Sci. (2014)

Bottom Line: In stromal cells, miR-143 enhanced collagen type III expression in normal gastric fibroblasts and cancer-associated fibroblasts through activation of transforming growth factor-β)/SMAD signaling.Furthermore, high miR-143 expression in GC was associated with worse cancer-specific mortality (P = 0.0141).These data suggest that miR-143 regulates fibrosis of scirrhous type GC through induction of collagen expression in stromal fibroblasts and that miR-143 expression serves as a prognostic marker of GC.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

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MicroRNA-143 (miR-143) expression in scirrhous type gastric cancer (GC) tissue and cell lines. In situ hybridization of miR-143 was carried out in combination with immunofluorescence staining in scirrhous type GC. MicroRNA-143 labeling was revealed by Cy3-conjugated streptavidin (red). (a) α-Smooth muscle actin (α-SMA), (b) vimentin, or (c) CAM5.2 labeling was revealed by FITC-conjugated secondary antibody (green). DNA was counterstained with DAPI (blue). MicroRNA-143 expression was localized to α-SMA-positive and vimentin-positive stromal fibroblasts. (d) MicroRNA-143 expression levels were evaluated in GC cell lines and fibroblasts. Bars and error bars indicate median and standard error, respectively. *P < 0.05. CaF, cancer-associated fibroblasts; NF, normal gastric fibroblasts.
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fig02: MicroRNA-143 (miR-143) expression in scirrhous type gastric cancer (GC) tissue and cell lines. In situ hybridization of miR-143 was carried out in combination with immunofluorescence staining in scirrhous type GC. MicroRNA-143 labeling was revealed by Cy3-conjugated streptavidin (red). (a) α-Smooth muscle actin (α-SMA), (b) vimentin, or (c) CAM5.2 labeling was revealed by FITC-conjugated secondary antibody (green). DNA was counterstained with DAPI (blue). MicroRNA-143 expression was localized to α-SMA-positive and vimentin-positive stromal fibroblasts. (d) MicroRNA-143 expression levels were evaluated in GC cell lines and fibroblasts. Bars and error bars indicate median and standard error, respectively. *P < 0.05. CaF, cancer-associated fibroblasts; NF, normal gastric fibroblasts.

Mentions: To elucidate why scirrhous-type GC possesses high miR-143 expression, we first investigated the localization of miR-143 expression in scirrhous type GC tissue by in situ hybridization of miR-143 in combination with immunostaining using markers for epithelial cells (CAM5.2), stromal fibroblasts (vimentin), and CaFs (α-SMA; Fig. 2a–c, Fig. S1).(30) Cancer fibroblasts, also termed myofibroblasts or activated fibroblasts, are well known as a major component of cancer stroma and play an important role in the regulation of cancer cell proliferation and metastasis.(5,30) In cancerous regions, double staining revealed that expression of miR-143 was observed in α-SMA- or vimentin-positive fibroblastic cells (Fig. 2a,b) but was not colocalized with CAM5.2-positive cancer cells (Fig. 2c). However, in non-neoplastic regions, miR-143 was highly expressed in normal epithelial cells, but the expression was faint or not present in stromal fibroblasts in non-neoplastic tissue (data not shown). Expression of miR-143 was also examined in 9 GC cell lines, as well as in NFs and CaFs. Expression of miR-143 was evident in NFs and CaFs, but was undetectable in GC cell lines (Fig. 2d). Moreover, the expression levels of miR-143 were higher in CaFs than in NFs, and CaFs derived from scirrhous type GC showed a tendency toward higher expression of miR-143 (Fig. 2d). These data indicated that miR-143 is localized to epithelial cells in normal gastric tissue, but its localization is changed to surrounding stromal fibroblasts, but not cancer cells, in scirrhous type GC.


MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer.

Naito Y, Sakamoto N, Oue N, Yashiro M, Sentani K, Yanagihara K, Hirakawa K, Yasui W - Cancer Sci. (2014)

MicroRNA-143 (miR-143) expression in scirrhous type gastric cancer (GC) tissue and cell lines. In situ hybridization of miR-143 was carried out in combination with immunofluorescence staining in scirrhous type GC. MicroRNA-143 labeling was revealed by Cy3-conjugated streptavidin (red). (a) α-Smooth muscle actin (α-SMA), (b) vimentin, or (c) CAM5.2 labeling was revealed by FITC-conjugated secondary antibody (green). DNA was counterstained with DAPI (blue). MicroRNA-143 expression was localized to α-SMA-positive and vimentin-positive stromal fibroblasts. (d) MicroRNA-143 expression levels were evaluated in GC cell lines and fibroblasts. Bars and error bars indicate median and standard error, respectively. *P < 0.05. CaF, cancer-associated fibroblasts; NF, normal gastric fibroblasts.
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fig02: MicroRNA-143 (miR-143) expression in scirrhous type gastric cancer (GC) tissue and cell lines. In situ hybridization of miR-143 was carried out in combination with immunofluorescence staining in scirrhous type GC. MicroRNA-143 labeling was revealed by Cy3-conjugated streptavidin (red). (a) α-Smooth muscle actin (α-SMA), (b) vimentin, or (c) CAM5.2 labeling was revealed by FITC-conjugated secondary antibody (green). DNA was counterstained with DAPI (blue). MicroRNA-143 expression was localized to α-SMA-positive and vimentin-positive stromal fibroblasts. (d) MicroRNA-143 expression levels were evaluated in GC cell lines and fibroblasts. Bars and error bars indicate median and standard error, respectively. *P < 0.05. CaF, cancer-associated fibroblasts; NF, normal gastric fibroblasts.
Mentions: To elucidate why scirrhous-type GC possesses high miR-143 expression, we first investigated the localization of miR-143 expression in scirrhous type GC tissue by in situ hybridization of miR-143 in combination with immunostaining using markers for epithelial cells (CAM5.2), stromal fibroblasts (vimentin), and CaFs (α-SMA; Fig. 2a–c, Fig. S1).(30) Cancer fibroblasts, also termed myofibroblasts or activated fibroblasts, are well known as a major component of cancer stroma and play an important role in the regulation of cancer cell proliferation and metastasis.(5,30) In cancerous regions, double staining revealed that expression of miR-143 was observed in α-SMA- or vimentin-positive fibroblastic cells (Fig. 2a,b) but was not colocalized with CAM5.2-positive cancer cells (Fig. 2c). However, in non-neoplastic regions, miR-143 was highly expressed in normal epithelial cells, but the expression was faint or not present in stromal fibroblasts in non-neoplastic tissue (data not shown). Expression of miR-143 was also examined in 9 GC cell lines, as well as in NFs and CaFs. Expression of miR-143 was evident in NFs and CaFs, but was undetectable in GC cell lines (Fig. 2d). Moreover, the expression levels of miR-143 were higher in CaFs than in NFs, and CaFs derived from scirrhous type GC showed a tendency toward higher expression of miR-143 (Fig. 2d). These data indicated that miR-143 is localized to epithelial cells in normal gastric tissue, but its localization is changed to surrounding stromal fibroblasts, but not cancer cells, in scirrhous type GC.

Bottom Line: In stromal cells, miR-143 enhanced collagen type III expression in normal gastric fibroblasts and cancer-associated fibroblasts through activation of transforming growth factor-β)/SMAD signaling.Furthermore, high miR-143 expression in GC was associated with worse cancer-specific mortality (P = 0.0141).These data suggest that miR-143 regulates fibrosis of scirrhous type GC through induction of collagen expression in stromal fibroblasts and that miR-143 expression serves as a prognostic marker of GC.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Show MeSH
Related in: MedlinePlus