title: Cancer cell contact causes oscillatory and polarized rise of cytoplasmic ionized calcium concentration in human umbilical vein endothelial cells.
abstract: The rise of cytoplasmic ionized Ca2+ concentration ([Ca2+]i) is an important factor in cellular signal transduction, which regulates a variety of cellular functions in vascular endothelial cells (vECs) such as morphological change, secretion of vaso-active molecules, or endothelial permeability. It is also known that the loss of vEC integrity plays pivotal roles in several physiological or pathological phenomena, such as inflammation or cancer metastasis. The aim of this study was to clarify the mode of cancer cell induced vEC retraction by cell to cell contact. Digital imaging analysis using Ca2+ indicator, fluo-3, clearly demonstrated an oscillatory intracellular and intercellular [Ca2+]i wave originated from the site of human breast cancer cell line MCF-7 cell contact in HUVECs, which was not inhibited by extracellular Ni2+ and was inhibited by pretreating the cells by paraformaldehyde. Although this phenomenon could be observed in malignant cells including murine malignant melanoma cell line, BL6, as well as benign cells including human fibroblast cell line, WI38, inert neutrophils did not cause vEC retraction nor [Ca2+]i oscillation. Thus, cancer cells could activate vECs by a cell to cell contact to cause retraction via common property of non-blood cells.
authors.affiliation: Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka 565-0871, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.forename: Hideo
authors.initials: H
authors.lastname: Ariyoshi
authors.forename: Masato
authors.initials: M
authors.lastname: Sakon
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Aono
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ueda
authors.forename: Masaru
authors.initials: M
authors.lastname: Tokunaga
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D018920:Coculture Techniques; D003593:Cytoplasm / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D009504:Neutrophils / Q000166:cytology; D014407:Tumor Cells, Cultured
chemical_list: D002118:Calcium