Endothelin-1 is an autocrine/paracrine growth factor for human cancer cell lines

Masayoshi Shichiri, Yukio Hirata, Tohru Nakajima, Kenji Ando, Taihei Imai, Masashi Yanagisawa, Tomoh Masaki, Fumiaki Marumo

Research output: Contribution to journalArticle

195 Citations (Scopus)

Abstract

We studied whether a novel vasoconstrictor peptide, endothelin-1 (ET-1), is synthesized by and released from human carcinoma cell lines, and whether ET-1 stimulates proliferation of these tumor cells. ET-1-like immunoreactivity was released from both HeLa and HEp-2 cells as a function of time. Reverse-phase HPLC of the conditioned media from HeLa cells revealed a major peak coeluting with standard ET-1. Northern blot analysis demonstrated the expression of mRNA for ET-1 precursor in both tumor cell lines. Both cell lines contained a single class of specific binding sites for ET-1. ET-1 dose-dependently induced increases in cytosolic free Ca2+ concentration in fura-2-loaded tumor cells, whose effect was completely abolished by chelating extracellular Ca2+ or by Ca2+-channel blocker. ET-1 stimulated proliferation of the quiescent cell lines in a dose-dependent manner, whose effect was inhibited by Ca2+-channel blocker. Polyclonal antibody for ET-1 inhibited proliferation of these cell lines, whereas nonimmune serum had no effect. These results demonstrate that ET-1 is synthesized by and released from human epithelial carcinoma cell lines, and that exogenous and endogenous ET-1 stimulates proliferation of the cells possibly through Ca2+ influx, suggesting its role as an autocrine/paracrine growth factor for certain tumor cells.

Original languageEnglish (US)
Pages (from-to)1867-1871
Number of pages5
JournalJournal of Clinical Investigation
Volume87
Issue number5
StatePublished - May 1991

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Endothelin-1
Intercellular Signaling Peptides and Proteins
Cell Line
Neoplasms
Cell Proliferation
Carcinoma
Fura-2
Vasoconstrictor Agents
Conditioned Culture Medium
Tumor Cell Line
HeLa Cells
Northern Blotting
Epithelial Cells
Binding Sites
High Pressure Liquid Chromatography
Messenger RNA
Peptides

Keywords

  • Cell proliferation
  • Cystolic free Ca concentration
  • Northern blot analysis
  • Radioimmunoassay
  • Receptor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Shichiri, M., Hirata, Y., Nakajima, T., Ando, K., Imai, T., Yanagisawa, M., ... Marumo, F. (1991). Endothelin-1 is an autocrine/paracrine growth factor for human cancer cell lines. Journal of Clinical Investigation, 87(5), 1867-1871.

Endothelin-1 is an autocrine/paracrine growth factor for human cancer cell lines. / Shichiri, Masayoshi; Hirata, Yukio; Nakajima, Tohru; Ando, Kenji; Imai, Taihei; Yanagisawa, Masashi; Masaki, Tomoh; Marumo, Fumiaki.

In: Journal of Clinical Investigation, Vol. 87, No. 5, 05.1991, p. 1867-1871.

Research output: Contribution to journalArticle

Shichiri, M, Hirata, Y, Nakajima, T, Ando, K, Imai, T, Yanagisawa, M, Masaki, T & Marumo, F 1991, 'Endothelin-1 is an autocrine/paracrine growth factor for human cancer cell lines', Journal of Clinical Investigation, vol. 87, no. 5, pp. 1867-1871.
Shichiri M, Hirata Y, Nakajima T, Ando K, Imai T, Yanagisawa M et al. Endothelin-1 is an autocrine/paracrine growth factor for human cancer cell lines. Journal of Clinical Investigation. 1991 May;87(5):1867-1871.
Shichiri, Masayoshi ; Hirata, Yukio ; Nakajima, Tohru ; Ando, Kenji ; Imai, Taihei ; Yanagisawa, Masashi ; Masaki, Tomoh ; Marumo, Fumiaki. / Endothelin-1 is an autocrine/paracrine growth factor for human cancer cell lines. In: Journal of Clinical Investigation. 1991 ; Vol. 87, No. 5. pp. 1867-1871.
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