Effect of CD133 overexpression on bone metastasis in prostate cancer cell line LNCaP

Sohn,Hong  Moon; Kim,Bora; Park,Mineon; Ko,Young  Jong; Moon,Yeon  Hee; Sun,Jae  Myung; Jeong,Byung‑Cheol; Kim,Young  Wook; Lim,Wonbong

doi:10.3892/ol.2019.10443

Effect of CD133 overexpression on bone metastasis in prostate cancer cell line LNCaP

Authors:
- Hong Moon Sohn
- Bora Kim
- Mineon Park
- Young Jong Ko
- Yeon Hee Moon
- Jae Myung Sun
- Byung‑Cheol Jeong
- Young Wook Kim
- Wonbong Lim
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Affiliations: Department of Orthopaedic Surgery, Chosun University Hospital, Dong-Gu, Gwangju 61453, Republic of Korea, Department of Dental Hygiene, Chodang University, Muan County, Jeollanam‑do 58530, Republic of Korea, Department of Medicine, College of Medicine, Chosun University, Dong-gu, Gwangju 61452, Republic of Korea
Published online on: June 6, 2019 https://doi.org/10.3892/ol.2019.10443
Pages: 1189-1198
Copyright: © Sohn et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prostate cancer (PC) metastasizes to the bone, and a small number of cancer cells, described as cancer stem cells (CSCs), have the ability to differentiate into tumor cells. CSCs are responsible for tumor recurrence and metastases. In the present study, we examined whether ectopic overexpression of CD133, a key molecule maintaining the stability of CSCs in the human PC cell line, LnCaP, caused bone metastasis in a mouse model. Ectopic overexpression of CD133 was induced in LnCaP cells, and CSC‑related protein expression was measured. Furthermore, a colony‑forming assay was performed to compare results against the blank green fluorescent protein‑expressing cells. Furthermore, epithelial to mesenchymal transition‑related protein expression, cell migration and wound healing were investigated. To assess the role of CD133 in bone metastasis, CD133‑overexpressing LnCaP cells were inoculated into mice via intracardiac injection, and bone metastasis was assessed via histological and immunohistochemical study. In addition, cytokine arrays were used to determine the cytokines involved in bone metastasis. Ectopic overexpression of CD133 in LnCaP cells increased CSC properties such as Oct‑4 and Nanog expression and colony‑forming ability. Furthermore, epithelial‑to‑mesenchymal transition (EMT) properties, including decreased E‑cadherin and increased vimentin expression, wound gap distance, and cell migration increased. CD133 overexpression led to formation of bone metastatic tumors in mice, consistent with results of hematoxylin and eosin staining. In addition, an increase in expression of the macrophage‑migration inhibitory factor was observed at the tumor margin in mice inoculated with CD133+ LNCaP cells. These findings suggest a regulatory role of CD133 in stem cell and EMT properties, and the sustained acquisition of osteolytic features in PC. Therefore, our results may facilitate development of a novel classification system and therapeutic strategies for bone metastasis of PC.

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