TOV112D Xenograft Model Overview

The TOV112D xenograft model is derived from a human ovarian carcinoma cell line, specifically established from a patient with high-grade serous ovarian cancer. This model is widely used in preclinical research to investigate the molecular mechanisms of ovarian cancer, test novel therapeutic strategies, and study the development of drug resistance. High-grade serous ovarian cancer is the most aggressive and common subtype of ovarian carcinoma, known for its poor prognosis and rapid development of resistance to platinum-based chemotherapy. The TOV112D xenograft model is valuable for evaluating therapies targeting the molecular pathways that drive ovarian tumorigenesis and for studying the tumor microenvironment’s role in disease progression and metastasis.

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Biological and Molecular Characteristics

TOV112D cells express various surface markers associated with ovarian carcinoma, including epithelial markers like cytokeratins and epithelial membrane antigen (EMA). These cells are known to exhibit mutations in key tumor suppressor genes such as TP53, contributing to their high proliferative capacity and resistance to apoptosis. TOV112D cells are also characterized by their sensitivity to platinum-based chemotherapies, including cisplatin and carboplatin, which makes the model ideal for testing new agents designed to overcome chemotherapy resistance. Additionally, the model exhibits dysregulation in the PI3K/AKT and MAPK/ERK signaling pathways, which contribute to the survival, proliferation, and metastasis of ovarian cancer cells. The TOV112D xenograft model is particularly useful for evaluating agents targeting these pathways and investigating strategies to sensitize tumors to chemotherapy.

Marker	Expression Level	Function
Cytokeratin	High	Epithelial cell marker
EMA	High	Epithelial membrane antigen
TP53	Mutated	Tumor suppressor gene involved in apoptosis
PI3K/AKT pathway	Dysregulated	Promotes cell survival and proliferation

In Vivo Model Development and Tumorigenicity

The TOV112D xenograft model is typically developed by implanting TOV112D cells into immunocompromised mice, such as NOD/SCID or NSG mice, which lack functional T and B cells. Upon implantation, the cells form rapidly growing tumors that replicate the key characteristics of human ovarian carcinoma, including high cellularity, frequent necrosis, and significant vascularization. The tumors also exhibit characteristics such as solid and cystic regions, similar to those seen in ovarian serous carcinoma. The model is frequently used to test the efficacy of chemotherapeutic agents, particularly platinum-based therapies like cisplatin and carboplatin, as well as other potential treatments aimed at overcoming chemotherapy resistance.

In addition to subcutaneous implantation, orthotopic implantation of TOV112D cells into the ovarian bursa of immunocompromised mice can be performed to replicate the natural site of tumor growth and metastasis. This orthotopic model provides a more clinically relevant environment for studying tumor progression, peritoneal dissemination, and metastatic spread to distant organs like the liver and lymph nodes.

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Histopathology and Immunohistochemical Profile

Histopathological analysis of TOV112D xenografts reveals a highly cellular tumor with large pleomorphic cells and regions of necrosis, reflecting the rapid growth of the tumor. The tumors often exhibit a mixture of solid and cystic areas, which is typical of ovarian carcinoma. Immunohistochemical staining of TOV112D xenografts shows high expression of cytokeratin and EMA, confirming the epithelial origin of the tumor. Additionally, strong expression of TP53 is observed, indicating the mutation of this critical tumor suppressor gene, which contributes to the tumor’s resistance to chemotherapy. The tumors also exhibit high levels of Ki-67, a marker of cell proliferation, further indicating the aggressive nature of the model. CD31 staining reveals high vascularity within the tumors, highlighting the importance of angiogenesis in supporting tumor growth. The model is also characterized by markers of immune evasion and the tumor microenvironment, making it suitable for evaluating immunotherapy strategies.

Preclinical Applications and Drug Response

The TOV112D xenograft model is widely used to evaluate the efficacy of various therapeutic agents, particularly those targeting ovarian cancer’s hallmark molecular pathways. Given the model’s initial sensitivity to platinum-based chemotherapy, it is particularly valuable for testing combination therapies aimed at overcoming chemotherapy resistance. The model is frequently used to evaluate novel chemotherapies, targeted therapies, and immune-based treatments.

One of the primary applications of the TOV112D model is to investigate therapies that target the PI3K/AKT and MAPK/ERK signaling pathways, which are often dysregulated in ovarian cancer. In addition, the model is valuable for testing agents that inhibit angiogenesis, such as anti-VEGF (vascular endothelial growth factor) therapies, due to the tumors’ reliance on blood vessel formation for growth. The TOV112D model is also increasingly used in preclinical trials to evaluate the effectiveness of immunotherapies, including immune checkpoint inhibitors and monoclonal antibodies targeting tumor-associated antigens, such as CA-125, which is often elevated in ovarian cancer patients.

The model’s ability to develop resistance to platinum-based chemotherapy makes it an important tool for evaluating novel agents that aim to overcome drug resistance and improve patient outcomes in ovarian cancer treatment.

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To request the TOV112D xenograft model for your preclinical studies, please use the form below. A customized quote and additional model specifications will be provided upon inquiry.

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