title: Cleaved CD147 shed from the surface of malignant melanoma cells activates MMP2 produced by fibroblasts.
abstract: BACKGROUND
  Cluster of differentiation 147 (CD147)/basigin on the malignant tumor cell surface is critical for tumor proliferation, invasiveness, metastasis, and angiogenesis. CD147 expressed on malignant melanoma cells can induce tumor cell invasion by stimulating the production of matrix metalloproteinases (MMPs) by surrounding fibroblasts. Membrane vesicles, microvesicles and exosomes have attracted attention, as vehicles of functional molecules and their association with CD147 has been reported. Cleaved CD147 fragments released from tumor cells were reported to interact with fibroblasts. We investigated the intercellular mechanisms by which CD147 stimulates fibroblasts to induce MMP2 activity.
  
  
  METHODS
  CD147 was knocked-down using short hairpin RNA (shRNA). The stimulatory effect of CD147 in cell culture supernatants, microvesicles, and exosomes on the enzymatic activity of MMP2 was examined by gelatin zymography.
  
  
  RESULTS
  Supernatants from A375 control cells induced increased enzymatic activity of fibroblasts; such activity was significantly lower in CD147 knock-down cells.
  
  
  CONCLUSIONS
  Cleaved CD147 plays a pivotal role in stimulating fibroblasts to induce MMP2 activity.
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Hatanaka
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan higashiy@m.kufm.kagoshima-u.ac.jp.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Higashi
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fukushige
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Baba
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Department of Laboratory and Vascular Medicine, Cardiovascular and Respiratory Disorders, Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Teruto
authors.initials: T
authors.lastname: Hashiguchi
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, P.R. China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Kanekura
mesh_terms: D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: C497886:BSG protein, human; D034741:RNA, Small Interfering; D051926:Basigin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: CD147; exosomes; malignant melanoma; matrix metalloproteinases; microvesicles