Open Access

Connective tissue growth factor produced by cancer‑associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma

  • Authors:
    • Yuuki Ohara
    • Atsushi Enomoto
    • Yuta Tsuyuki
    • Kotaro Sato
    • Tadashi Iida
    • Hiroki Kobayashi
    • Yasuyuki Mizutani
    • Yuki Miyai
    • Akitoshi Hara
    • Shinji Mii
    • Jun Suzuki
    • Kyoko Yamashita
    • Fumiya Ito
    • Yashiro Motooka
    • Nobuaki Misawa
    • Takayuki Fukui
    • Koji Kawaguchi
    • Kohei Yokoi
    • Shinya Toyokuni
  • View Affiliations

  • Published online on: July 3, 2020     https://doi.org/10.3892/or.2020.7669
  • Pages: 838-848
  • Copyright: © Ohara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Malignant mesothelioma is an aggressive neoplasm for which effective treatments are lacking. We often encounter mesothelioma cases with a profound desmoplastic reaction, suggesting the involvement of cancer‑associated fibroblasts (CAFs) in mesothelioma progression. While the roles of CAFs have been extensively studied in other tumors and have led to the view that the cancer stroma contains heterogeneous populations of CAFs, their roles in mesothelioma remain unknown. We previously showed that connective tissue growth factor (CTGF), a secreted protein, is produced by both mesothelioma cells and fibroblasts and promotes the invasion of mesothelioma cells in vitro. In this study, we examined the clinical relevance of CAFs in mesothelioma. Using surgical specimens of epithelioid malignant pleural mesothelioma, we evaluated the clinicopathological significance of the expression of α‑smooth muscle actin (αSMA), the most widely used marker of CAFs, the expression of CTGF, and the extent of fibrosis by immunohistochemistry and Elastica‑Masson staining. We also analyzed the expression of mesenchymal stromal cell‑ and fibroblast‑expressing Linx paralogue (Meflin; ISLR), a recently reported CAF marker that labels cancer‑restraining CAFs and differ from αSMA‑positive CAFs, by in situ hybridization. The extent of fibrosis and CTGF expression in mesothelioma cells did not correlate with patient prognosis. However, the expression of αSMA and CTGF, but not Meflin, in CAFs correlated with poor prognosis. The data suggest that CTGF+ CAFs are involved in mesothelioma progression and represent a potential molecular target for mesothelioma therapy.
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September-2020
Volume 44 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ohara Y, Enomoto A, Tsuyuki Y, Sato K, Iida T, Kobayashi H, Mizutani Y, Miyai Y, Hara A, Mii S, Mii S, et al: Connective tissue growth factor produced by cancer‑associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma. Oncol Rep 44: 838-848, 2020
APA
Ohara, Y., Enomoto, A., Tsuyuki, Y., Sato, K., Iida, T., Kobayashi, H. ... Toyokuni, S. (2020). Connective tissue growth factor produced by cancer‑associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma. Oncology Reports, 44, 838-848. https://doi.org/10.3892/or.2020.7669
MLA
Ohara, Y., Enomoto, A., Tsuyuki, Y., Sato, K., Iida, T., Kobayashi, H., Mizutani, Y., Miyai, Y., Hara, A., Mii, S., Suzuki, J., Yamashita, K., Ito, F., Motooka, Y., Misawa, N., Fukui, T., Kawaguchi, K., Yokoi, K., Toyokuni, S."Connective tissue growth factor produced by cancer‑associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma". Oncology Reports 44.3 (2020): 838-848.
Chicago
Ohara, Y., Enomoto, A., Tsuyuki, Y., Sato, K., Iida, T., Kobayashi, H., Mizutani, Y., Miyai, Y., Hara, A., Mii, S., Suzuki, J., Yamashita, K., Ito, F., Motooka, Y., Misawa, N., Fukui, T., Kawaguchi, K., Yokoi, K., Toyokuni, S."Connective tissue growth factor produced by cancer‑associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma". Oncology Reports 44, no. 3 (2020): 838-848. https://doi.org/10.3892/or.2020.7669