Establishment from a human chondrosarcoma of a new immortal cell line with high tumorigenicity <i>in vivo</i>, which is able to form proteoglycan‐rich cartilage‐like nodules and to respond to insulin <i>in vitro</i>

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公開日
1991-07-09
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/ijc.2910480515
公開者
Wiley

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<jats:title>Abstract</jats:title><jats:p>The human chondrosarcoma cell line (HCS‐2/8) established by our group expresses cartilage phenotypes such as production of cartilage‐type proteoglycans and collagen type II, but its tumorigenicity is low. To develop an <jats:italic>in vitro</jats:italic> experimental system for studies of human chondrosarcomas, a new immortal cell line of human chondrosarcoma, named HCS‐2/A, was established from the same tumor. HCS‐2/A cells proliferated with a doubling time of 3° days in a medium containing 20% fetal bovine serum (FBS). This growth rate was comparable to that of HCS‐2/8 cells. However, HCS‐2/A cells proliferated more rapidly than HCS‐2/8 cells in the presence of 2–10% FBS. Like HCS‐2/8 cells, HCS‐2/A cells had a polygonal shape in sparse cultures and became spherical as they reached confluence, after which they formed nodules composed of multi‐layered cells and a large quantity of extracellular matrix showing strong metachromasia. The nodules formed by HCS‐2/A cells were thicker and also larger in diameter than those formed by HCS‐2/8 cells. Electron microscopically, the cells in the nodules resembled chondrocytes <jats:italic>in vivo</jats:italic>, but each cell had an irregular‐shaped nucleus which is a characteristic of tumor cells. The cells actively synthesized “cartilage‐specific” large proteoglycans and their level of proteoglycan synthesis was comparable to that of HCS‐2/8 cells. Insulin, which stimulates proteoglycan and DNA syntheses in cultured chondrocytes, markedly Increased proteoglycan synthesis in HCS‐2/A cells. On the other hand, the hormone only slightly increased proteoglycan synthesis in HCS‐2/8 cells. Insulin also stimulated DNA synthesis in cultured HCS‐2/A cells, but not in HCS‐2/8 cells. Immunostaining revealed that HCS‐2/A cells produced type‐11 collagen but not type‐1 collagen. However, the level of collagen synthesis of HCS‐2/A cells was lower than that of HCS‐2/8 cells. Inoculation of HCS‐2/A cells into athymic mice resulted in the formation of chondrosarcomas that grew faster than those arising from HCS‐2/8 cells.</jats:p>

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