Epithelial ovarian carcinoma (EOC) patients often acquire resistance against common chemotherapeutic drugs like paclitaxel and cisplatin. The mechanism responsible for the same is ambiguous. We have identified a putative drug-resistant tumour cell phenotype (EpCAM⁺CD45⁺) in the ascitic fluid of EOC patients, which appears to originate from the primary tumour. These cells represent the major tumour burden and are more drug resistant compared to EpCAM⁺ tumour cells due to the over-expression of SIRT1, ABCA1 and BCL2 genes. We have found that the entire EpCAM⁺CD45⁺ population is highly invasive with signature mesenchymal gene expression and also consists of subpopulations of ovarian cancer stem cells (CD133⁺ and CD117⁺CD44⁺). Additionally, we demonstrate that the EpCAM⁺CD45⁺ tumour cells over-express major histocompatibility complex class I antigen, which enable them to evade the natural killer cell-mediated immune surveillance. Preliminary evidence obtained in OVCAR-5 cells suggests that exosomes, secreted by non-tumour cells of the ascitic fluid, play an important role in rendering drug resistance and invasive properties to the cancer cells. Identification of such aggressive tumour cells and deciphering their origin is important for designing better drug targets for EOC.

中文翻译：

---

侵袭性浆液性上皮性卵巢癌可能通过EpCAM + CD45 +表型传播。

上皮性卵巢癌（EOC）患者通常对常见的化疗药物如紫杉醇和顺铂耐药。造成这种情况的机制是模棱两可的。我们在EOC患者的腹水中发现了一种推定的耐药性肿瘤细胞表型（EpCAM ⁺ CD45 ⁺），它似乎起源于原发肿瘤。与SICAM ⁺肿瘤细胞相比，这些细胞代表了主要的肿瘤负担，并且由于SIRT1，ABCA1和BCL2基因的过表达而具有更高的耐药性。我们已经发现，整个EpCAM ⁺ CD45 ⁺群体具有标志性间充质基因表达的高度侵袭性，并且还由卵巢癌干细胞亚群（CD133⁺和CD117 ⁺ CD44 ⁺）。此外，我们证明EpCAM ⁺ CD45 ⁺肿瘤细胞过表达主要的组织相容性复合物I类抗原，这使它们能够逃避自然杀伤细胞介导的免疫监视。在OVCAR-5细胞中获得的初步证据表明，由腹水的非肿瘤细胞分泌的外泌体在赋予癌细胞抗药性和侵袭特性方面起着重要作用。鉴定此类侵袭性肿瘤细胞并破译它们的起源对于为EOC设计更好的药物靶标非常重要。