细胞外基质蛋白保护小细胞肺癌细胞免于凋亡：小细胞肺癌在体内生长和耐药的一种机制。

Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo.

作者信息

Sethi T, Rintoul R C, Moore S M, MacKinnon A C, Salter D, Choo C, Chilvers E R, Dransfield I, Donnelly S C, Strieter R, Haslett C

机构信息

Respiratory Medicine Unit, Rayne Laboratory, University of Edinburgh Medical School, Scotland, UK.

出版信息

Nat Med. 1999 Jun;5(6):662-8. doi: 10.1038/9511.

DOI:10.1038/9511

PMID:10371505

Abstract

Resistance to chemotherapy is a principal problem in the treatment of small cell lung cancer (SCLC). We show here that SCLC is surrounded by an extensive stroma of extracellular matrix (ECM) at both primary and metastatic sites. Adhesion of SCLC cells to ECM enhances tumorigenicity and confers resistance to chemotherapeutic agents as a result of beta1 integrin-stimulated tyrosine kinase activation suppressing chemotherapy-induced apoptosis. SCLC may create a specialized microenvironment, and the survival of cells bound to ECM could explain the partial responses and local recurrence of SCLC often seen clinically after chemotherapy. Strategies based on blocking beta1 integrin-mediated survival signals may represent a new therapeutic approach to improve the response to chemotherapy in SCLC.

摘要

化疗耐药是小细胞肺癌（SCLC）治疗中的一个主要问题。我们在此表明，SCLC在原发部位和转移部位均被广泛的细胞外基质（ECM）基质所包围。SCLC细胞与ECM的黏附增强了致瘤性，并赋予对化疗药物的耐药性，这是由于β1整合素刺激的酪氨酸激酶激活抑制了化疗诱导的细胞凋亡。SCLC可能会创造一个特殊的微环境，与ECM结合的细胞的存活可以解释临床上SCLC化疗后常见的部分缓解和局部复发。基于阻断β1整合素介导的存活信号的策略可能代表一种新的治疗方法，以改善SCLC对化疗的反应。