Epithelial to mesenchymal transition might be induced via CD44 isoform switching in colorectal cancer

Mashita, Naoki; Yamada, Suguru; Nakayama, Goro; Tanaka, Chie; Iwata, Nakao; Kanda, Mitsuro; Kobayashi, Daisuke; Fujii, Tsutomu; Sugimoto, Hiroyuki; Koike, Masahiko; Nomoto, Shuji; Fujiwara, Michitaka; Kodera, Yasuhiro

doi:10.1002/jso.23705

Cited by 32 publications

(27 citation statements)

References 35 publications

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“…In a study of colorectal cancer, the standard isoform CD44s seemed to be correlated with EMT, but higher CD44 expression predicted poor survival in that study in contrast to our results in ovarian cancer [26]. …”

Section: Discussioncontrasting

confidence: 96%

MMP-14 and CD44 in Epithelial-to-Mesenchymal Transition (EMT) in ovarian cancer

et al. 2016

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Background: To investigate the expression of MMP-14 and CD44 as well as epithelial-to-mesenchymal transition(EMT)-like changes in ovarian cancer and to determine correlations with clinical outcome. Methods: In 97 patients with ovarian cancer, MMP-14 and CD44 expression as determined by immunohistochemistry was investigated in relation to EMT-like changes. To determine this, immunohistochemical staining of E-cadherin and vimentin was performed. Results: Patients with expression of both MMP-14 and CD44 in their tumors had a poor prognosis despite complete debulking. Serous histology in advanced-stage tumors (FIGO IIB-IV) correlated with CD44 (rho .286, p < 0.01). Also, CD44 correlated with percentage vimentin expression (rho .217, p < 0.05). In logistic regression analysis with complete debulking as the outcome parameter, CD44 expression was found to be significant (OR 3,571 (95 % Confidence Interval 1,112-11,468) p = 0.032), though this was not the case for MMP-14 and EMT parameters. Conclusion: The subgroup of patients with double expression of MMP-14 and CD44 had a poor prognosis despite complete debulking. Serous subtype in advanced-stage patients and CD44 expression were found to be correlated with vimentin expression, and CD44 expression was found to be significantly correlated with complete debulking. However, a significant correlation between EMT and clinical parameters was not found.

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Section: Discussioncontrasting

confidence: 96%

MMP-14 and CD44 in Epithelial-to-Mesenchymal Transition (EMT) in ovarian cancer

et al. 2016

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“…A switch from CD44v to CD44s is essential for EMT and tumour progression in breast cancer (Brown et al , 2011). Furthermore, the ratio of vimentin/E-cadherin mRNA expression is significantly correlated with the CD44s/CD44v9 ratio in colorectal cancer, indicating that CD44 switching might induce EMT (Mashita et al , 2014). These findings suggest that CD44s confers mesenchymal properties, unlike other CD44-variants, and is associated with metastasis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of CD44-positive cancer stem-like cells at the invasive front of gastric cancer

et al. 2016

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Background:The invasive tumour front may provide prognostic information. We examined the relationship between the presence of cancer stem cells (CSCs) at the invasive tumour front and prognosis in gastric cancer (GC).Methods:CD44 is a CSC marker; accordingly, CD44 standard (CD44s), CD44 variant-6 (CD44v6), and CD44 variant-9 (CD44v9) expression were examined in 123 resected primary GCs and the clinical significance of CSCs at the invasive tumour front was analysed.Results:Thirteen (10.6%), 79 (64.2%), and 47 (38.2%) GCs were CD44s-, CD44v6-, and CD44v9-positive, respectively. Patients with CD44-positive expression at the invasive tumour front had significantly poorer disease-specific survival than those with negative expression (CD44s: P<0.00001, CD44v6: P=0.013, CD44v9: P=0.0002). CD44s expression at the invasive tumour front was an independent prognostic factor in resectable GC patients (hazard ratio=3.13; 95% confidence interval, 1.09–9.01; P=0.035) and was significantly associated with peritoneal (P<0.001), lymphatic (P<0.001), and haematogenous recurrences (P=0.008). In addition, the number of CD44 isoforms expressed in cancer cells at the invasive tumour front was associated with patient prognosis. No conventional clinicopathological factors were independently associated with CD44 expression at the invasive tumour front.Conclusions:CD44-positive cancer stem-like cells at the invasive tumour front indicate poor survival and can be a unique biological prognostic factor for GC.

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“…The expression of E-cadherin was previously shown to be repressed when ZEB1, ZEB2, or Snail bound to the E-box elements of CDH1, which encodes E-cadherin. 8,9) The down-regulated expression of E-cadherin is characterized by the loss of cell-cell adhesion and acquisition of a migratory phenotype. Mashita et al reported that the expression levels of standard CD44 isoform (CD44s) mRNA/variant 9 isoform (CD44v9) mRNA (CD44s/CD44v9) ratio were higher in the cells of mesenchymal phenotype than those of epithelial phenotype.…”

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confidence: 99%

Induction of Epithelial-Mesenchymal Transition and Down-Regulation of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells

Tanaka

Hosokawa

Yonezawa

et al. 2015

Biological & Pharmaceutical Bulletin

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Epithelial-mesenchymal transition (EMT) and changes in the expression of the microRNA-200 (miR-200) family were examined in the human colorectal cancer (CRC) cell line SW620 with acquired oxaliplatin (L-OHP) resistance. Two CRC cell lines, SW480, derived from primary CRC, and SW620, derived from lymph node metastasis, which were obtained from the same patient, were used in the present study. L-OHP-resistant SW620 cells were obtained by exposure to L-OHP for 155 d. The concentration of L-OHP was increased to 80 µM in a stepwise manner. The IC50 value of L-OHP was increased 16-fold in L-OHP-resistant SW620 cells, which also displayed mesenchymal cell-like characteristics, such as the down-regulation of E-cadherin and up-regulation of vimentin. However, L-OHP-resistant SW480 cells were not obtained when the concentration of L-OHP was increased in a similar stepwise manner. The expression levels of members of the miR-200 family (miR-200a, miR-200b, miR-429, miR-200c, and miR-141) were significantly higher in SW480 cells than in SW620 cells. The expression levels of miR-200c and miR-141 were significantly lower in L-OHP-resistant SW620 cells than in control SW620 cells. L-OHP-resistant SW620 cells did not exhibit cross-resistance to other anti-cancer drugs used to treat CRC, such as 5-fluorouracil, irinotecan, and the active metabolite of irinotecan (SN-38). These results suggest that the down-regulated expression of miR-200c and miR-141 plays a role in selective resistance to L-OHP and EMT in CRC cells during repeated treatments with L-OHP.

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Epithelial to mesenchymal transition might be induced via CD44 isoform switching in colorectal cancer

Abstract: The status of EMT and CD44 is a critical prognostic factor, with CD44 isoform switching a possible trigger for EMT in CRC.

Cited by 32 publications

References 35 publications

MMP-14 and CD44 in Epithelial-to-Mesenchymal Transition (EMT) in ovarian cancer

MMP-14 and CD44 in Epithelial-to-Mesenchymal Transition (EMT) in ovarian cancer

Prognostic impact of CD44-positive cancer stem-like cells at the invasive front of gastric cancer

Induction of Epithelial-Mesenchymal Transition and Down-Regulation of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells

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