Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2

In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumori...

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Main Authors: Rizwan Ali, Hajar Al Zahrani, Tlili Barhoumi, Alshaimaa Alhallaj, Abdullah Mashhour, Musaad A. Alshammari, Yasser A. Alshawakir, Omar Baz, Abdullah H. Alanazi, Abdul Latif Khan, Hassan Al Nikhli, Mohammed A. Al Balwi, Lolwah Al Riyees, Mohamed Boudjelal
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/6/1303
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author Rizwan Ali
Hajar Al Zahrani
Tlili Barhoumi
Alshaimaa Alhallaj
Abdullah Mashhour
Musaad A. Alshammari
Yasser A. Alshawakir
Omar Baz
Abdullah H. Alanazi
Abdul Latif Khan
Hassan Al Nikhli
Mohammed A. Al Balwi
Lolwah Al Riyees
Mohamed Boudjelal
spellingShingle Rizwan Ali
Hajar Al Zahrani
Tlili Barhoumi
Alshaimaa Alhallaj
Abdullah Mashhour
Musaad A. Alshammari
Yasser A. Alshawakir
Omar Baz
Abdullah H. Alanazi
Abdul Latif Khan
Hassan Al Nikhli
Mohammed A. Al Balwi
Lolwah Al Riyees
Mohamed Boudjelal
Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2
Cells
breast cancer
cell line
KAIMRC2
triple negative
stem cells
metastatic
author_facet Rizwan Ali
Hajar Al Zahrani
Tlili Barhoumi
Alshaimaa Alhallaj
Abdullah Mashhour
Musaad A. Alshammari
Yasser A. Alshawakir
Omar Baz
Abdullah H. Alanazi
Abdul Latif Khan
Hassan Al Nikhli
Mohammed A. Al Balwi
Lolwah Al Riyees
Mohamed Boudjelal
author_sort Rizwan Ali
title Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2
title_short Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2
title_full Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2
title_fullStr Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2
title_full_unstemmed Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2
title_sort isolation and establishment of a highly proliferative, cancer stem cell-like, and naturally immortalized triple-negative breast cancer cell line, kaimrc2
publisher MDPI AG
series Cells
issn 2073-4409
publishDate 2021-05-01
description In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells’ expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.
topic breast cancer
cell line
KAIMRC2
triple negative
stem cells
metastatic
url https://www.mdpi.com/2073-4409/10/6/1303
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spelling doaj-55ec70febf3440cbb260404958dfd5af2021-06-01T00:56:44ZengMDPI AGCells2073-44092021-05-01101303130310.3390/cells10061303Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2Rizwan Ali0Hajar Al Zahrani1Tlili Barhoumi2Alshaimaa Alhallaj3Abdullah Mashhour4Musaad A. Alshammari5Yasser A. Alshawakir6Omar Baz7Abdullah H. Alanazi8Abdul Latif Khan9Hassan Al Nikhli10Mohammed A. Al Balwi11Lolwah Al Riyees12Mohamed Boudjelal13King Abdullah International Medical Research Center (KAIMRC), Medical Research Core Facility and Platforms (MRCFP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi ArabiaKing Abdullah International Medical Research Center (KAIMRC), Medical Research Core Facility and Platforms (MRCFP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi ArabiaKing Abdullah International Medical Research Center (KAIMRC), Medical Research Core Facility and Platforms (MRCFP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi ArabiaKing Abdullah International Medical Research Center (KAIMRC), Medical Research Core Facility and Platforms (MRCFP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi ArabiaKing Abdullah International Medical Research Center (KAIMRC), Medical Research Core Facility and Platforms (MRCFP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaExperimental Surgery and Animal Lab, College of Medicine, King Saud University, Riyadh 11451, Saudi ArabiaKing Abdullah International Medical Research Center (KAIMRC), Medical Research Core Facility and Platforms (MRCFP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi ArabiaDepartment of Pathology and Laboratory Medicine, King Abdulaziz Medical City (KAMC), MNGHA, Riyadh 11426, Saudi ArabiaDepartment of Pathology and Laboratory Medicine, King Abdulaziz Medical City (KAMC), MNGHA, Riyadh 11426, Saudi ArabiaDepartment of Pathology and Laboratory Medicine, King Abdulaziz Medical City (KAMC), MNGHA, Riyadh 11426, Saudi ArabiaDepartment of Pathology and Laboratory Medicine, King Abdulaziz Medical City (KAMC), MNGHA, Riyadh 11426, Saudi ArabiaDepartment of Surgery, KAMC, MNGHA, Riyadh 11426, Saudi ArabiaKing Abdullah International Medical Research Center (KAIMRC), Medical Research Core Facility and Platforms (MRCFP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi ArabiaIn vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells’ expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.https://www.mdpi.com/2073-4409/10/6/1303breast cancercell lineKAIMRC2triple negativestem cellsmetastatic