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Cited by 59Cancer Cells and MetastasisPancreatic and Hepatic Oncology ResearchAngiogenesis and VEGF in Cancer

Expression of cancer-associated fibroblast markers in advanced colorectal cancer

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Nishishita, Rie, Morohashi, Satoko, Seino, Hiroko, Wu, Yunyan, Yoshizawa, Tadashi, Haga, Toshihiro, Saito, Kensuke, Hakamada, Kenichi +2 more·2018·Oncology Letters
DOI 10.3892/ol.2018.8097PMC PMC5876461
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Abstract

Colorectal cancer is one of the most common causes of mortality from cancer worldwide. Previous studies have demonstrated that cancer-associated fibroblasts (CAFs) promote neoangiogenesis and tumor growth for various tumors. The present study analyzed CAF markers, including α-smooth muscle actin (α-SMA), collagen I, platelet-derived growth factor receptor-β (PDGFR-β), and D2-40 (antibody recognizing podoplanin), and vessel markers, including cluster of differentiation (CD)31 and CD34, for 121 advanced colorectal cancer cases using a digital image analyzing technique. The association between CAF markers and vessel markers with clinicopathological factors was investigated. Furthermore, the association between CAF markers with each other, and their association with vessel markers was analyzed. Mean/median expression area of stromal and vessel markers in tumors were collagen I, 26.787%; D2-40, 1.372%; PDGFR-β, 11.646%; α-SMA-positive and desmin-negative myofibroblasts (α-SMA subtraction), 15.372%; CD31, 3.635%; and CD34, 2.226%. The expression area of α-SMA subtraction was significantly correlated with collagen I (P<0.001, correlation rho=0.509). High levels of α-SMA subtraction (P=0.002), collagen I (P=0.040), and PDGFR-β (P=0.040) expressions tended to be associated with high venous invasion. D2-40 did not correlate with other CAF and vessel markers. These results indicated that individual CAFs may have different expression patterns, and different strength effects for venous invasion in advanced colorectal cancer stroma.

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  • CAFs residing in the TME are heterogeneous cells with different origins, functions (pro- or anti-tumor activities), and surface markers such as α-SMA, MYL9, MYLK, MMP2, DCN, and COL1A2.

    “CAFs residing in TME are heterogeneous cells with different origins, different functions (pro or anti-tumor activities) and different surface markers such as alpha-smooth muscle actin (α-SMA), myosin light chain 9 (MYL9), myosin light chain kinase (MYLK), matrix metalloproteinase 2 (MMP2), decorin (DCN) and collagen type I alpha 2 (COL1A2) [60–63].”

    From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [62]

    The Introduction identifies α-SMA as a CAF marker, and the Discussion reports varying CAF-marker expression in advanced colorectal cancer. The paper does not establish different CAF origins or both pro- and anti-tumor activities, and it does not identify MYL9, MYLK, MMP2, DCN, or COL1A2 as CAF markers; it studies collagen I rather than COL1A2 specifically. (LLM, conf=0.88)

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Research works printed but not linked: 24

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Cited by

Sorted by citations

Authors
Nishishita, R., Morohashi, S., Seino, H., Wu, Y., Yoshizawa, T., Haga, T., Saito, K., Hakamada, K., Fukuda, S., & Kijima, H.
Affiliations
Hirosaki University (JP)
Corresponding author
Morohashi, Satoko
ORCID
Venue
Oncology Letters
Publisher
Spandidos Publications
Published
2018-02-21
Volume
15
Issue
5
Pages
6195-6202
ISSN
  • 1792-1074 (ISSN-L)
  • 1792-1082
DOI
10.3892/ol.2018.8097
PMC
PMC5876461
OpenAlex
W2793512221
Cited by
59
References
0
Citations by year
2025: 5 · 2024: 4 · 2023: 14 · 2022: 8 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 2
FWCI
2.63
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Oncology Letters (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology
  • Hirosaki University
  • Japan Society for the Promotion of Science (15K19763, 18K07702, 16K19328, 17K17575, 16K10448, 17H04057)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
cancer-associated fibroblasts, advanced colorectal cancer, tumor stroma, alpha-smooth muscle actin, type I collagen, PDGFRβ, D2-40, podoplanin, CD31, CD34, venous invasion, myofibroblasts, tumor angiogenesis

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