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Versican G1 and G3 domains are upregulated and latent transforming growth factor-β binding protein-4 is downregulated in breast cancer stroma

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Abstract

Background

Cancers are supported by a distinct type of stroma, and versican is overexpressed in the stroma of malignant tumors, including breast cancer. Versican interacts with hyaluronan and fibrillin-1 at its amino terminus (G1) and carboxyl terminus (G3), respectively. Fibrillin-1 also associates with latent transforming growth factor-β binding protein (LTBP)-1 and -4. The detailed alteration of these molecules in breast cancer tissues is still unclear.

Methods

In 18 patients, alteration of versican, fibrillin-1 and LTBP-1 and 4 was elucidated in comparison with matched normal tissues, using real-time reverse transcriptase polymerase chain reaction, slot blotting and immunohistochemistry. The relationship between the protein expression and clinicopathological features was also investigated.

Results

In breast cancer tissues, mRNAs for versican V1 and V0 were upregulated, and the extracted protein levels of the versican G1 and G3 domains were increased. Meanwhile, LTBP-4 was decreased, and fibrillin-1 and LTBP-1 remained unchanged. The immunohistochemical observations were consistent with the biochemical findings, and the molecules were localized in the stromal tissue rather than in the cancer cells themselves. The expression of versican G3 and G1 domains was positively related to the Ki67 index of carcinoma cells and tumor size, respectively.

Conclusion

The stromal alterations of versican and LTBP-4 might influence the carcinogenesis and progression of breast tumor cells and modulate their biological phenotypes.

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Authors and Affiliations

  1. Department of Pathology, Osaka Medical College, 2-7 Takatsuki, Osaka, 569-8686, Japan

    Yuko Takahashi, Hiroko Kuwabara & Yuro Shibayama

  2. Division of Breast Surgery, Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan

    Yuko Takahashi & Nobuhiko Tanigawa

  3. Department of Nursing and Health, School of Nursing and Health, Aichi Prefectural University, Aichi, Japan

    Masahiko Yoneda

  4. Department of Advanced Medicine, National Center for Geriatrics and Gerontology, Aichi, Japan

    Zenzo Isogai

Authors
  1. Yuko Takahashi
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  2. Hiroko Kuwabara
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  3. Masahiko Yoneda
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  4. Zenzo Isogai
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  5. Nobuhiko Tanigawa
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Correspondence to Hiroko Kuwabara.

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Takahashi, Y., Kuwabara, H., Yoneda, M. et al. Versican G1 and G3 domains are upregulated and latent transforming growth factor-β binding protein-4 is downregulated in breast cancer stroma. Breast Cancer 19, 46–53 (2012). https://doi.org/10.1007/s12282-011-0264-7

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  • DOI: https://doi.org/10.1007/s12282-011-0264-7

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