MDA-MB-231 (M D Anderson - Metastatic Breast - 231) is a human breast cancer cell line isolated at M D Anderson in 1973 that is used in therapeutic research, especially in the context of triple negative breast cancer. [1] [2]
MDA-MB-231 cells were derived from a pleural effusion due to an adenocarcinoma originating in a 51-year-old caucasian female. [2] The cell line is triple negative, meaning it lacks oestrogen receptors, progesterone receptors, and HER2 (human epidermal growth factor receptor 2) amplification which many current treatment options rely on making it difficult to cure. [3] [4] In addition, this cell line has a low expression of the Ki-67 proliferation marker, down regulation of claudin-3 and claudin-4, enrichment for markers associated with the epithelial-mesenchymal transition and the CD44+ CD24-/low phenotype associated with breast cancer stem cells and increased metastasis, [5] [6] [7] and is a mutant in the p53 and KRas oncogenes. [8] [9] The cells are considered biosafety level 1. They can be grown in 2 or 3-D cultures. [10]
MDA-MB-231 is used to study potential treatments for a cancer with currently limited treatment options by either improving current medication delivery and efficacy, [11] [12] or by trying new treatment courses. [13] [14]
This cell line has also been utilized to study metastasis to the bones [15] [16] and lungs. [16] [17]
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues.
The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis in cancer progression.
E-selectin, also known as CD62 antigen-like family member E (CD62E), endothelial-leukocyte adhesion molecule 1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a selectin cell adhesion molecule expressed only on endothelial cells activated by cytokines. Like other selectins, it plays an important part in inflammation. In humans, E-selectin is encoded by the SELE gene.
Triple-negative breast cancer (TNBC) is any breast cancer that either lacks or shows low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification. Triple-negative is sometimes used as a surrogate term for basal-like.
Leukotriene B4 receptor 2, also known as BLT2, BLT2 receptor, and BLTR2, is an Integral membrane protein that is encoded by the LTB4R2 gene in humans and the Ltbr2 gene in mice.
The basal-like carcinoma is a recently proposed subtype of breast cancer defined by its gene expression and protein expression profile.
Epithelial cell adhesion molecule (EpCAM), also known as CD326 among other names, is a transmembrane glycoprotein mediating Ca2+-independent homotypic cell–cell adhesion in epithelia. EpCAM is also involved in cell signaling, migration, proliferation, and differentiation. Additionally, EpCAM has oncogenic potential via its capacity to upregulate c-myc, e-fabp, and cyclins A & E. Since EpCAM is expressed exclusively in epithelia and epithelial-derived neoplasms, EpCAM can be used as diagnostic marker for various cancers. It appears to play a role in tumorigenesis and metastasis of carcinomas, so it can also act as a potential prognostic marker and as a potential target for immunotherapeutic strategies.
Zinc finger protein SNAI1 is a protein that in humans is encoded by the SNAI1 gene. Snail is a family of transcription factors that promote the repression of the adhesion molecule E-cadherin to regulate epithelial to mesenchymal transition (EMT) during embryonic development.
Breast cancer metastasis suppressor 1 is a protein that in humans is encoded by the BRMS1 gene.
MCF-7 is a breast cancer cell line isolated in 1970 from a 69-year-old White woman. MCF-7 is the acronym of Michigan Cancer Foundation-7, referring to the institute in Detroit where the cell line was established in 1973 by Herbert Soule and co-workers. The Michigan Cancer Foundation is now known as the Barbara Ann Karmanos Cancer Institute.
Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer; there is no stage after IV.
Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1 gene.
In molecular biology, the miR-200 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by binding and cleaving mRNAs or inhibiting translation. The miR-200 family contains miR-200a, miR-200b, miR-200c, miR-141, and miR-429. There is growing evidence to suggest that miR-200 microRNAs are involved in cancer metastasis.
The tumor microenvironment is a complex ecosystem surrounding a tumor, composed of cancer cells, stromal tissue and the extracellular matrix. Mutual interaction between cancer cells and the different components of the tumor microenvironment support its growth and invasion in healthy tissues which correlates with tumor resistance to current treatments and poor prognosis. The tumor microenvironment is in constant change because of the tumor's ability to influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.
MDA-MB-468 is a cell line that was isolated from a 51-year-old female human in 1977, and is commonly used in breast cancer research. MDA-MB-468 cells were extracted from a pleural effusion of mammary gland and breast tissues, and have proven useful for the study of metastasis, migration, and breast cancer proliferation.
Patient derived xenografts (PDX) are models of cancer where the tissue or cells from a patient's tumor are implanted into an immunodeficient or humanized mouse. It is a form of xenotransplantation. PDX models are used to create an environment that allows for the continued growth of cancer after its removal from a patient. In this way, tumor growth can be monitored in the laboratory, including in response to potential therapeutic options. Cohorts of PDX models can be used to determine the therapeutic efficiency of a therapy against particular types of cancer, or a PDX model from a specific patient can be tested against a range of therapies in a 'personalized oncology' approach.
Breast cancer is the most prevalent type of cancer among women globally, with 685,000 deaths recorded worldwide in 2020. The most commonly used treatment methods for breast cancer include surgery, radiotherapy and chemotherapy. Some of these treated patients experience disease relapse and metastasis. The aggressive progression and recurrence of this disease has been attributed the presence of a subset of tumor cells known as breast cancer stem cells (BCSCs). These cells possess the abilities of self-renewal and tumor initiation, allowing them to be drivers of metastases and tumor growth. The microenvironment in which these cells reside is filled with residential inflammatory cells that provide the needed signaling cues for BCSC-mediated self-renewal and survival. The production of cytokines allows these cells to escape from the primary tumor and travel through the circulation to distant organs, commencing the process of metastasis. Due to their significant role in driving disease progression, BCSCs represent a new target by which to treat the tumor at the source of metastasis.
4T1 is a breast cancer cell line derived from the mammary gland tissue of a mouse BALB/c strain. 4T1 cells are epithelial and are resistant to 6-thioguanine. In preclinical research, 4T1 cells have been used to study breast cancer metastasis as they can metastasize to the lung, liver, lymph nodes, brain and bone. The cells are known to be highly aggressive in live tissues.
Relda Marie Cailleau was an American scientist primarily known for her establishment of a series of breast cancer cell lines that have been crucial to the discovery of anticancer drugs and to an understanding of breast cancer biology.
Ironomycin is a derivative of salinomycin and potent small molecule against persister cancer stem cells, that is under preclinical evaluation by SideROS for the treatment of cancer. Ironomycin was shown to induce ferroptosis in breast cancer cell lines and its mechanism of action involves the targeting of lysosomal iron.