CD10-bearing fibroblast inhibits matrigel invasive potency of interleukin-1α-producing squamous cell carcinoma by diminishing substance P levels in the tumor microenvironment

Lining Xie, Yoichi Moroi, Gaku Tsuji, Min Liu, Sayaka Hayashida, Masakazu Takahara, Shuji Fukagawa, Satoshi Takeuchi, Baoen Shan, Takeshi Nakahara, Uchi Hiroshi, Takehiko Yokomizo, Masutaka Furue

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

CD10 is a neutral endopeptidase, which cleaves various peptide substrates including substance P. CD10 expression has been detected in peritumoral fibroblasts (Fb) within the invasive area of various cancers such as squamous cell carcinoma (SCC). However, the biological significance of CD10-bearing Fb remains largely unknown. We examined dynamic interactions of Fb with tumorigenic A431 SCC cells or non-tumorigenic HaCaT squamous cells. The SCC and HaCaT cells did not synthesize CD10, while Fb constitutively expressed CD10. When co-cultured, SCC markedly upregulated fibroblastic CD10 expression compared with HaCaT, which was mainly attributable to SCC-derived interleukin-1α (IL-1α). Both SCC and Fb autonomously secreted substance P, which eventually enhanced the invasive capacity of SCC in a matrigel invasion assay by upregulating matrix metalloproteinase (MMP)-1 and MMP-2, but not MMP-9. Transfection of siRNA for CD10 successfully knocked down the CD10 expression in Fb (CD10ND-Fb). In the presence of CD10ND-Fb, substance P levels in supernatants as well as MMP production and the invasive potency of SCC were significantly augmented compared with control scramble RNA-transfected Fb. We also transfected CD10 vector to Fb and found that the matrigel invasive ability of SCC cells was downregulated co-cultured with CD10 vector-transfected Fb rather than empty vector-transfected Fb. In conclusion, the CD10-bearing Fb generated by SCC-derived IL-1 inhibited the invasive capacity of SCC by diminishing the microenvironmental concentration of substance P. (Cancer Sci 2010; 101: 2570-2578)

Original languageEnglish
Pages (from-to)2570-2578
Number of pages9
JournalCancer Science
Volume101
Issue number12
DOIs
Publication statusPublished - Dec 1 2010

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Tumor Microenvironment
Substance P
Interleukin-1
Squamous Cell Carcinoma
Fibroblasts
matrigel
Neprilysin
Matrix Metalloproteinase 1
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Small Interfering RNA
Transfection
Cultured Cells
Neoplasms
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

CD10-bearing fibroblast inhibits matrigel invasive potency of interleukin-1α-producing squamous cell carcinoma by diminishing substance P levels in the tumor microenvironment. / Xie, Lining; Moroi, Yoichi; Tsuji, Gaku; Liu, Min; Hayashida, Sayaka; Takahara, Masakazu; Fukagawa, Shuji; Takeuchi, Satoshi; Shan, Baoen; Nakahara, Takeshi; Hiroshi, Uchi; Yokomizo, Takehiko; Furue, Masutaka.

In: Cancer Science, Vol. 101, No. 12, 01.12.2010, p. 2570-2578.

Research output: Contribution to journalArticle

Xie, Lining ; Moroi, Yoichi ; Tsuji, Gaku ; Liu, Min ; Hayashida, Sayaka ; Takahara, Masakazu ; Fukagawa, Shuji ; Takeuchi, Satoshi ; Shan, Baoen ; Nakahara, Takeshi ; Hiroshi, Uchi ; Yokomizo, Takehiko ; Furue, Masutaka. / CD10-bearing fibroblast inhibits matrigel invasive potency of interleukin-1α-producing squamous cell carcinoma by diminishing substance P levels in the tumor microenvironment. In: Cancer Science. 2010 ; Vol. 101, No. 12. pp. 2570-2578.
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AU - Xie, Lining

AU - Moroi, Yoichi

AU - Tsuji, Gaku

AU - Liu, Min

AU - Hayashida, Sayaka

AU - Takahara, Masakazu

AU - Fukagawa, Shuji

AU - Takeuchi, Satoshi

AU - Shan, Baoen

AU - Nakahara, Takeshi

AU - Hiroshi, Uchi

AU - Yokomizo, Takehiko

AU - Furue, Masutaka

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