Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/20085
標題: OSMR異型受體在非小細胞肺癌中的表現
Expression of Oncostatin M receptor β subunit (OSMRβ) isoform in non-small cell lung cancer
作者: 楊秀卿
Yang, Hsiu-Ching
關鍵字: OSM;OSM;OSMR;lung cancer;OSMR;肺癌
出版社: 生物醫學研究所
摘要: 
Oncostatin M (OSM) is a multifunctional cytokine of interleukin-6 (IL-6) family, and mediates its bioactivities through two different heterodimer receptors. Both kinds of receptors involve gp130 as signal transducing intermediate, which dimerizes with either leukemia inhibitory receptor LIFRβ or with OSMRβ to generate, respectively, type Ι and type ΙΙ OSM receptors. In vitro, LIF can inhibit embryonic stem cell differentiation and induce acute phase protein synthesis in hepatocytes. Although OSM behaves like LIF, it displays other specific characteristics, such as inhibiting the growth of a variety of solid tumor cells, and such activities are not shared with LIFR or other IL-6 family receptors.
Three mRNA sequences of OSMR have been documented in NCBI database, and they could encode the OSMRβ (NM003999) and OSMRs (BC010943 and BC063468) proteins. By protein sequence analysis, we showed that OSMRβ might span across the plasma membrane at amino acid sequences 1-18 and 740-760, and with its C terminus suspended in cytosol to mediate signal transduction to the downstream molecules. By contrast, the OSMRs proteins were anchored outside the plasma membrane at amino acid sequences 1-18 without the second transmembrane motif.
Our experiments demonstrated that both OSMRβ and OSMRs were expressed in all 7 lung cancer cell lines; however, OSMRs was barely expressed in H1437 cell line. By studying OSM effect on H1437 cells, which constitutively express OSMRβ but not OSMRs, and on H2087 cells, of which both OSMRβ and OSMRs were abundantly expressed, we found that growth of H1437 cells was inhibited at high cell concentration, whereas that of H2087 cells was unaffected after OSM treatment. Furthermore, OSM also causes H1437 and H2087 cells scattered and helps maintaining cell morphology in crescent shape for a period of time. These different effects on H1437 and H2087 cells suggest that OSM may normally transduce signal via OSMRβ whereas OSMRs may act as a decoy receptor in non-small cell lung cancer.

OSM是一種多功能性的細胞激素,它可藉由與受體的專一性接合來引發標的細胞的許多生理反應。OSM的受體分為兩種:其中第一類型OSM受體由gp130與LIFRβ所構成,可以與OSM或是LIF結合;而第二類型OSM受體則由gp130與OSMRβ所組成,它是OSM的專一性受體。透過第一類型受體,OSM可在標的細胞中引發一系列與LIF類似的細胞生理反應;而透過第二類型受體,OSM則可對標的細胞產生較為特殊的影響,像是抑制許多實體固態腫瘤的生長等等,這部分透過第二類型受體所活化的細胞生理反應與LIF或是其它IL-6家族細胞激素所引起的細胞生理反應是完全不同的。
根據美國國家生物技術資訊網站所公布之OSMR cDNA序列,顯示出目前已經發現了三個OSMR的相關序列,這些序列可能產生三個不同大小的蛋白,也就是說,OSMRβ可能具有數種不同的異型受體次單位。在本實驗中,我們進行了OSMR蛋白序列分析,發現OSMRβ可能利用其第1-18及740-760這兩段序列,將蛋白嵌插於細胞膜上,並使得含有功能性蛋白結合位置的C端暴露於細胞質內。然而,另外二個較小的OSMRs則可能是藉由第1-18的胺基酸序列,將其懸掛在細胞膜外側。
使用OSM分別刺激大量表現OSMRβ及OSMRs的H2087細胞,以及穩定表現OSMRβ但不表現OSMRs的H1437細胞,我們發現當肺癌細胞生長至一定程度後,OSM的刺激可能會使其停止生長,並向周圍遷移,使得原本聚集成團生長之細胞,顯現出四散的情形。此外,實驗中也顯示出這些由OSM對於肺癌細胞所引發的生理反應,可能是透過OSMRβ這個受體次單位來進行調控的,而OSMRs在這些肺癌細胞內,則可能是扮演著拮抗的角色,因此幾乎不表現OSMRs的H1437細胞對於OSM的刺激較為敏感,而大量表現OSMRs的H2087細胞則對OSM的刺激較無反應。由以上的結果,我們推測肺癌細胞內的OSMRs可能是這些細胞為了中和OSM對於它們所產生的影響而製造出來的一種誘餌蛋白。
URI: http://hdl.handle.net/11455/20085
Appears in Collections:生物醫學研究所

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