Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cell Cycle. 2012 Jun 1;11(11):2107-13. doi: 10.4161/cc.20544.
Recent studies have suggested that some ovarian and pelvic serous carcinomas could originate from the fimbriated end of the distal fallopian tube. To test this hypothesis, we immortalized a normal human fallopian tube epithelial (FTE) cell line by using retrovirus-mediated overexpression of the early region of the SV40 T/t antigens and the human telomerase reverse transcriptase subunit (hTERT). These immortalized FTEs were then transformed by ectopic expression of oncogenic human HRAS (V12) . Tumorigenicity of the immortalized and/or transformed cells was subsequently tested by anchorage-independence growth assay and inoculation into nude mice via subcutaneous and intraperitoneal injection. As expected, the HRAS (V12) -transformed FTEs produced tumors through both subcutaneous and intraperitoneal injections, whereas no tumor growth was observed in immortalized FTEs. Unexpectedly, histopathological examination of tumors resulting from subcutaneous as well as intraperitoneal injections revealed largely poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma. The tumor implants invaded extensively to the liver, colon, spleen, omentum, adrenal gland and renal capsule. Immunohistochemical staining of tumor cells showed positive staining for the epithelial cell markers cytokeratin AE1/AE3 and Müllerian lineage marker PAX8. Our study demonstrates that FTEs can generate poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma through genetic modifications. Thus, we provide the first experimental evidence that fimbrial epithelial cells of the fallopian tube could be a potential source of ovarian mucinous adenocarcinoma.
最近的研究表明，一些卵巢和盆腔浆液性癌可能起源于输卵管远端的伞端。为了验证这一假说，我们通过逆转录病毒介导的 SV40 T/t 抗原早期区域和人端粒酶逆转录酶亚单位（hTERT）的过表达，使正常的人输卵管上皮（FTE）细胞系永生化。然后，通过异位表达致癌的人 HRAS（V12）使这些永生化的 FTE 转化。随后通过锚定独立性生长测定和通过皮下和腹腔内注射接种到裸鼠中来测试永生化和/或转化细胞的致瘤性。正如预期的那样，HRAS（V12）转化的 FTE 通过皮下和腹腔内注射均可产生肿瘤，而永生化的 FTE 则没有观察到肿瘤生长。出乎意料的是，皮下和腹腔内注射产生的肿瘤的组织病理学检查显示出大量低分化黏液性腺癌与未分化癌混合。肿瘤植入物广泛侵袭肝脏、结肠、脾脏、大网膜、肾上腺和肾包膜。肿瘤细胞的免疫组织化学染色显示上皮细胞标志物细胞角蛋白 AE1/AE3 和 Müllerian 谱系标志物 PAX8 的阳性染色。我们的研究表明，FTE 可以通过遗传修饰产生低分化黏液性腺癌与未分化癌混合。因此，我们提供了第一个实验证据，表明输卵管的伞端上皮细胞可能是卵巢黏液性腺癌的潜在来源。
