Autocrine activation of PDGFRα promotes the progression of ovarian cancer
Autocrine activation of PDGFRα promotes the progression of ovarian cancer
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DOI：
10.1038/sj.onc.1209232
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发表时间：
2006-03-01
期刊：
影响因子：
8
通讯作者：
Donner, DB
中科院分区：
文献类型：
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作者：
Matei, D;Emerson, RE;Donner, DB
血小板源性生长因子受体（PDGFR）α在卵巢癌细胞和肿瘤中表达。这导致我们测试卵巢癌是否也产生这种受体的配体，因为这将证明这种恶性肿瘤通过自分泌激活支持自身生长和扩散。我们用RT-PCR、免疫组化（IHC）和ELISA检测了PDGFR配体在卵巢肿瘤、细胞系和腹腔液中的表达。我们在大多数卵巢肿瘤中检测到PDGFR α配体的强mRNA表达。在47例卵巢肿瘤中，分别有34例和32例通过免疫组化检测了受体和配体（PDGFR α和PDGF AB）的表达。PDGFR α和PDGF AB的染色强相关（P值= 0.014），表明自分泌环在卵巢癌中起作用。通过ELISA定量腹膜液中的PDGF AA和BB。两种配体在卵巢癌腹水标本（n = 54）中的分泌水平高于非恶性疾病（n = 8）的液体。在卵巢癌细胞的条件培养基中检测到PDGF。这种条件培养基诱导PDGFR、Akt和MAPK的活化并刺激细胞增殖。中和PDGF抗体阻断了这些作用。通过siRNA或针对受体的中和抗体的特异性PDGFR抑制抑制了PDGF刺激的受体活化和细胞增殖，表明受体靶向在卵巢癌治疗中具有作用。
Platelet-derived growth factor receptor ( PDGFR) a expression was found in ovarian cancer cells and tumors by microarray hybridization. This led us to test whether ovarian cancers also produce ligands for this receptor, as this would demonstrate that such malignancies support their own growth and spread through autocrine activation. We assayed the expression of ligands for the PDGFR in ovarian tumors, cell lines and peritoneal fluid using RT-PCR, immunohistochemistry (IHC) and ELISA. We detected strong mRNA expression for the PDGFR alpha ligands in most ovarian tumors. Receptor and ligand expressions (PDGFR alpha and PDGF AB) were also detected by IHC in, respectively, 34 and 32 of 47 ovarian tumors. The stainings for PDGFR alpha and PDGF AB were strongly correlated (P-value = 0.014), suggesting that an autocrine loop is functional in ovarian cancer. PDGF AA and BB were quantified in peritoneal fluid by ELISA. Both ligands are secreted at higher levels in ovarian cancer ascites specimens (n = 54) than in fluid from nonmalignant disorders (n = 8). PDGF was detected in media conditioned by ovarian cancer cells. Such conditioned media induced activation of the PDGFR, Akt and MAPK and stimulated cell proliferation. A neutralizing PDGF antibody blocked these effects. Specific PDGFR inhibition by siRNA or a neutralizing antibody to the receptor inhibited PDGF-stimulated receptor activation and cell proliferation, suggesting that receptor targeting has a role in ovarian cancer treatment.