WNT1 Inducible Signaling Pathway Protein 1 Is a Stroma-Specific Secreting Protein Inducing a Fibroblast Contraction and Carcinoma Cell Growth in the Human Prostate.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      CCN Intercellular Signaling Proteins*/genetics ; CCN Intercellular Signaling Proteins*/metabolism ; Cell Transformation, Neoplastic*/genetics ; Cell Transformation, Neoplastic*/metabolism ; Fibroblasts*/metabolism ; Fibroblasts*/pathology ; Prostatic Neoplasms*/genetics ; Prostatic Neoplasms*/pathology ; Proto-Oncogene Proteins*/genetics ; Proto-Oncogene Proteins*/metabolism; Cadherins ; Carcinoma/metabolism ; Carcinoma/pathology ; Cell Proliferation/genetics ; Cell Proliferation/physiology ; Connective Tissue Growth Factor ; Culture Media, Conditioned/pharmacology ; Humans ; Male ; Prostate/metabolism ; Prostate/pathology ; Signal Transduction ; Tumor Necrosis Factor-alpha/pharmacology ; Vimentin/metabolism
    • Abstract:
      The WNT1 inducible signaling pathway protein 1 (WISP1), a member of the connective tissue growth factor family, plays a crucial role in several important cellular functions in a highly tissue-specific manner. Results of a RT-qPCR indicated that WISP1 expressed only in cells of the human prostate fibroblasts, HPrF and WPMY-1, but not the prostate carcinoma cells in vitro. Two major isoforms (WISP1v1 and WISP1v2) were identified in the HPrF cells determined by RT-PCR and immunoblot assays. The knock-down of a WISP1 blocked cell proliferation and contraction, while treating respectively with the conditioned medium from the ectopic WISP1v1- and WISPv2-overexpressed 293T cells enhanced the migration of HPrF cells. The TNFα induced WISP1 secretion and cell contraction while the knock-down of WISP1 attenuated these effects, although TNFα did not affect the proliferation of the HPrF cells. The ectopic overexpression of WISP1v1 but not WISP1v2 downregulated the N-myc downstream regulated 1 (NDRG1) while upregulating N-cadherin, slug, snail, and vimentin gene expressions which induced not only the cell proliferation and invasion in vitro but also tumor growth of prostate carcinoma cells in vivo. The results confirmed that WISP1 is a stroma-specific secreting protein, enhancing the cell migration and contraction of prostate fibroblasts, as well as the proliferation, invasion, and tumor growth of prostate carcinoma cells.
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    • Grant Information:
      109-2320-B-182-018-MY3 National Science and Technology Council, Taiwan; 110-2314-B-182-038-MY3 National Science and Technology Council, Taiwan; 111-2320-B-182-006-MY2 National Science and Technology Council, Taiwan; 110-2811-B-182-518 National Science and Technology Council, Taiwan; BMRP278 Linkou Chang Gung Memorial Hospital; D1I0111-3 Linkou Chang Gung Memorial Hospital
    • Contributed Indexing:
      Keywords: EMT; WISP1; contraction; proliferation; prostate; stroma; tumorigenesis
    • Accession Number:
      0 (CCN Intercellular Signaling Proteins)
      0 (CCN4 protein, human)
      0 (Cadherins)
      0 (Culture Media, Conditioned)
      0 (Proto-Oncogene Proteins)
      0 (Tumor Necrosis Factor-alpha)
      0 (Vimentin)
      139568-91-5 (Connective Tissue Growth Factor)
    • Publication Date:
      Date Created: 20221014 Date Completed: 20221017 Latest Revision: 20221019
    • Publication Date:
      20221213
    • Accession Number:
      PMC9570503
    • Accession Number:
      10.3390/ijms231911437
    • Accession Number:
      36232736