Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: molecular phenotype of chemoresistant ovarian tumors.
Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: molecular phenotype of chemoresistant ovarian tumors.
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DOI：
10.1371/journal.pone.0046858
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ahmed N
中科院分区：
文献类型：
--
作者：
Latifi A;Luwor RB;Bilandzic M;Nazaretian S;Stenvers K;Pyman J;Zhu H;Thompson EW;Quinn MA;Findlay JK;Ahmed N
腹水中的肿瘤细胞是卵巢癌患者疾病复发的主要来源。为了鉴定和分析从卵巢癌患者获得的腹水细胞群体，开发了一种新的方法来分离培养物中的粘附（AD）和非粘附（NAD）细胞。本研究招募了25名患者; 11名化疗无效（CN）和14名化疗耐药（CR）。来自CN和CR患者的AD细胞均表现出间充质形态，具有间充质干细胞和成纤维细胞的抗原谱。相反，NAD细胞具有上皮形态，癌抗原125（CA 125）、上皮细胞粘附分子（EpCAM）和细胞角蛋白7的表达增强。NAD细胞在腹膜内（i. p.）注射到裸鼠中，而AD细胞保持非致瘤性长达20周。CN和CR患者的AD和NAD群体之间的选择性上皮、间充质和癌症干细胞（CSC）标志物的随后比较证明了CR患者的NAD群体中E-钙粘蛋白、EpCAM、STAT 3和Oct 4的mRNA表达的增强趋势。在CR患者的AD人群中观察到CD 44、MMP 9和Oct 4的mRNA表达增强的类似趋势。因此，使用一种新的纯化方法，我们首次证明了腹水细胞分化为上皮致瘤性和间充质非致瘤性细胞群。我们还表明，从CR患者的腹水细胞主要是上皮细胞，并显示出增加的趋势与CSC相关的基因的mRNA表达，从CN患者的腹水分离的细胞相比。由于卵巢癌患者腹水中的肿瘤细胞在疾病复发中起主导作用，因此彻底了解CR和CN患者腹水微环境的生物学对于有效的治疗干预至关重要。
Tumor cells in ascites are a major source of disease recurrence in ovarian cancer patients. In an attempt to identify and profile the population of ascites cells obtained from ovarian cancer patients, a novel method was developed to separate adherent (AD) and non-adherent (NAD) cells in culture. Twenty-five patients were recruited to this study; 11 chemonaive (CN) and 14 chemoresistant (CR). AD cells from both CN and CR patients exhibited mesenchymal morphology with an antigen profile of mesenchymal stem cells and fibroblasts. Conversely, NAD cells had an epithelial morphology with enhanced expression of cancer antigen 125 (CA125), epithelial cell adhesion molecule (EpCAM) and cytokeratin 7. NAD cells developed infiltrating tumors and ascites within 12–14 weeks after intraperitoneal (i.p.) injections into nude mice, whereas AD cells remained non-tumorigenic for up to 20 weeks. Subsequent comparison of selective epithelial, mesenchymal and cancer stem cell (CSC) markers between AD and NAD populations of CN and CR patients demonstrated an enhanced trend in mRNA expression of E-cadherin, EpCAM, STAT3 and Oct4 in the NAD population of CR patients. A similar trend of enhanced mRNA expression of CD44, MMP9 and Oct4 was observed in the AD population of CR patients. Hence, using a novel purification method we demonstrate for the first time a distinct separation of ascites cells into epithelial tumorigenic and mesenchymal non-tumorigenic populations. We also demonstrate that cells from the ascites of CR patients are predominantly epithelial and show a trend towards increased mRNA expression of genes associated with CSCs, compared to cells isolated from the ascites of CN patients. As the tumor cells in the ascites of ovarian cancer patients play a dominant role in disease recurrence, a thorough understanding of the biology of the ascites microenvironment from CR and CN patients is essential for effective therapeutic interventions.
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影响因子：
3.5
作者：
Antolovic D;Galindo L;Carstens A;Rahbari N;Büchler MW;Weitz J;Koch M
通讯作者：
Koch M
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
9.3
作者：
Kandala PK;Srivastava SK
通讯作者：
Srivastava SK
DOI：
10.1111/igc.0b013e3181a8331f
发表时间：
2009-07-01
影响因子：
4.8
作者：
Bellone, Stefania;Siegel, Eric R.;Santin, Alessandro D.
通讯作者：
Santin, Alessandro D.
影响因子：
--
作者：
Kenny, Hilary A.;Dogan, Songuel;Zillhardt, Marion;Mitra, Anirban K.;Yamada, S. Diane;Krausz, Thomas;Lengyel, Ernst
通讯作者：
Lengyel, Ernst