title: Autocrine Prolactin Stimulates Endometrial Carcinoma Growth and Metastasis and Reduces Sensitivity to Chemotherapy.
abstract: Advanced and recurrent endometrial carcinoma (EC) exhibits a poor response to chemotherapy and low survival rates. It has been previously reported that human prolactin (hPRL) is upregulated in endometrial cancer and is associated with worse survival outcomes. We provide evidence for the functional role of hPRL in EC progression. We generated a model for the study of autocrine hPRL-mediated cell functional effects through the forced expression of hPRL in human EC cells. Autocrine hPRL expression stimulated cell proliferation, anchorage-independent growth, migration, and invasion of EC cells and promoted tumor growth, local invasion, and metastatic colonization in xenograft models. In addition, forced expression of hPRL decreased sensitivity of EC cells to chemotherapeutic drugs (i.e., doxorubicin and paclitaxel), both in vitro and in vivo. Consistently, small interfering RNA-mediated depletion of hPRL significantly reduced oncogenicity and enhanced the chemosensitivity of EC cells. As CD24 is hPRL-regulated and has been implicated in drug resistance in EC, we further showed that CD24 is a critical mediator of hPRL-stimulated reduced sensitivity to doxorubicin and paclitaxel in EC cells. Therefore, inhibition of hPRL signaling is a potential therapeutic strategy for the treatment of late-stage EC, which can be used in combination with chemotherapy to improve the chemotherapeutic response.
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.|Department of Pathology, Anhui Medical University, Hefei, Anhui 230000, China.
authors.forename: Keshuo
authors.initials: K
authors.lastname: Ding
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore 117599.
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Chong
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Yulu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Kong
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Pengxu
authors.initials: P
authors.lastname: Qian
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Zirui
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore 117599.
authors.forename: Vijay
authors.initials: V
authors.lastname: Pandey
authors.affiliation: Tsinghua-Berkeley Shenzhen Institute and Division of Life Sciences and Health, Tsinghua University Graduate School, Shenzhen 518055, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pathology, Anhui Medical University, Hefei, Anhui 230000, China.
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore 117599.|Tsinghua-Berkeley Shenzhen Institute and Division of Life Sciences and Health, Tsinghua University Graduate School, Shenzhen 518055, China.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lobie
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.|Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019898:Autocrine Communication / Q000187:drug effects; D018269:Carcinoma, Endometrioid / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D011388:Prolactin; D017239:Paclitaxel