The Human EPCAM (Epithelial Cell Adhesion Molecule) gene encodes a cell surface glycoprotein that plays a crucial role in cell adhesion and signaling. EPCAM is highly expressed in epithelial cells and is involved in the maintenance of tissue integrity and the regulation of epithelial cell differentiation.
The MC38 cell line, derived from C57BL6 murine colon adenocarcinoma cells, has been engineered to stably express the Human EPCAM gene. This stable cell line provides a model for studying the role of EPCAM in epithelial cell function and its potential as a target for cancer therapy. Researchers can use this cell line to investigate the effects of EPCAM on cell adhesion, migration, and signaling, as well as its role in tumor progression and metastasis.
Cancer immunotherapy has demonstrated significant therapeutic success in recent years. The researchers looked into the effectiveness of VV-EpCAM BiTE, a recombinant vaccinia virus that encodes an EpCAM-targeting bispecific T-cell engager (BiTE), in changing the tumor microenvironment (TME) to boost antitumor immunity across solid tumors. VV-EpCAM BiTE invaded and lysed malignant cells with high efficiency, boosting EpCAM BiTE secretion. This facilitated the interaction between EpCAM-positive tumor cells and CD3ϵ on T cells, activating naive T cells and causing cytokine release (e.g., IFN-γ, IL-2). Intratumoral delivery of VV-EpCAM BiTE significantly increased anticancer efficacy in tumors with high EpCAM expression, which was associated with increased immune cell infiltration, reduced CD8+ T cell exhaustion, and improved T-cell-mediated immune responses in the TME. These findings support VV-EpCAM BiTE's potential as a treatment method that combines bispecific antibody advantages with oncolytic virus capabilities.
Figure 1. The effect of EPCAM Stable Cell Line - MC38 on T-cell activation and cytotoxicity was assessed utilizing secreted EpCAM BiTE. The researchers evaluated T-cell activation markers CD69 and CD25, cytokine secretion (IFN-γ and IL-2), and T-cell cytotoxicity against 4T1, H22, MC38-EpCAM, and MC38 cells. (Wei M, et al., 2022)
Human EPCAM Stable Cell Line - MC38 could be a crucial tool in cancer biology, immunotherapy development, and molecular medicine due to EPCAM's (Epithelial Cell Adhesion Molecule) significant role in cancer progression, metastasis, and its potential as a therapeutic target. Here's a outline of applications:
(1) Cancer Biology and Metastasis Research:
EPCAM is overexpressed in many cancers and is associated with the proliferation, invasion, and metastasis of cancer cells. The Human EPCAM Stable Cell Line - MC38 could be utilized to study the mechanisms by which EPCAM contributes to these processes in a controlled environment. Researchers could knock down or overexpress EPCAM to observe its effects on cell behavior, facilitating a deeper understanding of its role in cancer biology. This could lead to the identification of new molecular targets for cancer therapy.
(2) Development of Targeted Therapies:
Given EPCAM's expression on the surface of many tumor cells, the Human EPCAM Stable Cell Line - MC38 offers a platform for developing and testing targeted therapies, including monoclonal antibodies and CAR-T cell therapies. Researchers can use this cell line to evaluate the efficacy of these therapies in vitro before progressing to in vivo models, speeding up the process of therapeutic development. This could also include screening for small molecules that inhibit EPCAM's function or expression, potentially offering a new class of cancer therapeutics.
(3) Tumor Microenvironment and Immunomodulation Studies:
EPCAM's role is not limited to tumor cells; it also affects the tumor microenvironment and interactions with the immune system. The Human EPCAM Stable Cell Line - MC38 could be used to study how EPCAM expression alters the immune response to tumors and to develop strategies that modulate this interaction to enhance immunotherapy outcomes. For instance, understanding how EPCAM expression on tumor cells influences T-cell activation or suppression could lead to new approaches to cancer immunotherapy that overcome immune evasion by tumors.
Customer Q&As
What specific methodologies were employed in the development and generation of this stable cell line?
A: The development of the Human EPCAM Stable Cell Line - MC38 involved transfecting MC38 cells with a plasmid containing the human EPCAM gene along with a selectable marker gene, typically antibiotic resistance. Following transfection, cells were subjected to selective pressure using the appropriate antibiotic to isolate those cells containing the desired gene. Subsequently, these selected cells were expanded and characterized to establish a stable cell line expressing human EPCAM.
Can you elucidate the specific role of EPCAM in cellular physiology and its relevance in cancer research?
A: EPCAM, or Epithelial Cell Adhesion Molecule, plays a multifaceted role in cellular physiology. It is involved in cell-cell adhesion, signaling, proliferation, migration, and differentiation. In cancer research, EPCAM is of particular interest due to its overexpression in various epithelial cancers, including colorectal, breast, and lung cancers. EPCAM's involvement in tumor growth, metastasis, and resistance to therapy makes it a potential therapeutic target and diagnostic marker in oncology research.
Could you provide insights into the genetic background of the MC38 cell line and its relevance to cancer research?
A: The MC38 cell line is derived from a murine colon adenocarcinoma model. It exhibits characteristics typical of colorectal cancer, making it a valuable tool for studying various aspects of cancer biology, including tumor development, progression, and response to treatment. MC38 cells have been extensively used in preclinical cancer research due to their immunogenicity and ability to form tumors in immunocompetent mice, facilitating studies on tumor immunology, immunotherapy, and tumor microenvironment interactions.
Could you elaborate on the functional assays used to assess the role of EPCAM in cellular processes?
A: Functional assays utilized to assess the role of EPCAM in cellular processes include cell proliferation assays, migration assays, adhesion assays, and assays evaluating signaling pathways associated with EPCAM. These assays provide insights into how EPCAM influences key cellular functions such as proliferation, migration, and adhesion, as well as its involvement in intracellular signaling cascades. Additionally, in vivo assays using mouse models may be employed to evaluate EPCAM's role in tumor growth, metastasis, and response to therapy within a physiological context.
Can you elaborate on the signaling pathways influenced by EPCAM expression in cancer cells?
A: EPCAM expression in cancer cells can influence various signaling pathways involved in tumor development and progression. One such pathway is the Wnt/β-catenin signaling pathway, where EPCAM interacts with β-catenin to regulate cell proliferation, migration, and stemness properties. Additionally, EPCAM can modulate EGFR (epidermal growth factor receptor) signaling, leading to increased cell survival and proliferation. Furthermore, EPCAM-mediated signaling crosstalk with other pathways such as MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) and PI3K/Akt (phosphatidylinositol-3-kinase/protein kinase B) pathways contributes to tumor growth, invasion, and metastasis.
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High specificity EPCAM expression
The Human EPCAM Stable Cell Line - MC38, through specific genetic engineering, stably expresses the human EPCAM protein, ensuring high specificity and consistent expression in tumor biology research, providing an accurate model for studying the role of EPCAM in tumor development and metastasis.
Facilitates tumor marker research
As EPCAM is an important marker for various cancers, the Human EPCAM Stable Cell Line - MC38 enables researchers to directly study the function of EPCAM in tumor formation and progression, accelerating the identification and validation of tumor markers.
Enhances data reproducibility
The stable expression of the Human EPCAM Stable Cell Line - MC38 ensures consistency and reproducibility of experimental results, providing a reliable data foundation for tumor-related research.
Accelerates drug screening and development
The Human EPCAM Stable Cell Line - MC38 can be used for high-throughput screening of antibodies or small molecule drugs, especially therapies targeting EPCAM, speeding up new drug discovery and the development of tumor treatment strategies.
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