VCaP Xenograft Model

VCaP Xenograft Model Overview

The VCaP xenograft model is derived from a human prostate cancer cell line, VCaP, which was established from a metastatic lesion in a patient with castration-resistant prostate cancer (CRPC). Prostate cancer is one of the most common cancers in men, and CRPC, characterized by the progression of prostate cancer despite androgen deprivation therapy, is a particularly challenging form of the disease. The VCaP xenograft model is highly valuable for preclinical studies, as it mirrors the molecular and metastatic features of human prostate cancer, providing a robust system to study tumor progression, androgen receptor (AR) signaling, metastasis, and therapeutic resistance. This model is especially important for evaluating androgen deprivation therapies, AR-targeted therapies, and new treatments for CRPC.

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Biological and Molecular Characteristics

VCaP cells are characterized by their androgen receptor (AR)-dependent growth, making them particularly relevant for studying AR signaling in prostate cancer. These cells also express high levels of prostate-specific antigen (PSA), a biomarker commonly used to monitor prostate cancer. In addition to AR signaling, VCaP cells harbor a TMPRSS2-ERG gene fusion, which is present in a subset of prostate cancer cases and plays a key role in tumor initiation and progression. VCaP cells are also known to exhibit alterations in the PI3K/AKT pathway, contributing to cell survival, proliferation, and resistance to therapy. The model is particularly useful for evaluating therapies that target the AR pathway, such as androgen receptor inhibitors and second-generation anti-androgens, as well as agents that target other key signaling pathways involved in tumor progression.

MarkerExpression LevelFunction
Androgen ReceptorHighKey driver of prostate cancer growth and progression
PSAElevatedProstate-specific biomarker for cancer monitoring
TMPRSS2-ERG FusionPresentGene fusion involved in tumor initiation and progression
PI3K/AKT pathwayDysregulatedPromotes cell survival and proliferation

In Vivo Model Development and Tumorigenicity

The VCaP xenograft model is typically established by implanting VCaP cells into immunocompromised mice, such as NOD/SCID or NSG mice, which lack functional T and B cells. Upon implantation, the cells form tumors that replicate the characteristics of human prostate cancer, including androgen receptor (AR)-dependent growth, tumorigenesis, and metastasis. The tumors exhibit high cellularity and significant vascularization, reflecting the rapid growth and angiogenic properties of the tumors. VCaP xenografts are particularly useful for studying androgen receptor signaling and evaluating therapies that target this pathway, including androgen deprivation therapies (ADT) and androgen receptor antagonists.

In addition to subcutaneous implantation, orthotopic models of VCaP can be established by implanting cells into the prostate gland of immunocompromised mice. This orthotopic model provides a more clinically relevant setting for studying tumor growth, local invasion, and metastatic spread, as prostate cancer is prone to metastasize to the lymph nodes, bones, and lungs. The ability of VCaP xenografts to replicate both primary tumor growth and metastasis makes them a valuable model for evaluating novel therapies aimed at reducing tumor progression and metastasis in CRPC.

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Histopathology and Immunohistochemical Profile

Histopathological analysis of VCaP xenografts reveals tumors with the characteristic features of prostate adenocarcinoma, including glandular structures and high mitotic activity. Immunohistochemical staining of VCaP xenografts shows strong expression of the androgen receptor (AR) in the tumor cells, confirming the androgen receptor-dependent nature of the tumor. Elevated levels of prostate-specific antigen (PSA) are also detected, reflecting the molecular profile of prostate cancer and the tumor’s relevance to clinical prostate cancer research. Additionally, VCaP xenografts show the presence of the TMPRSS2-ERG gene fusion, which can be detected through specific probes, further confirming the molecular characteristics of the tumor. The tumors also exhibit high levels of phosphorylated AKT, indicating the activation of the PI3K/AKT pathway, which contributes to tumor survival and resistance to therapy. The model’s high vascularity, assessed using CD31 staining, further supports the relevance of VCaP xenografts for studying angiogenesis and tumor growth.

Preclinical Applications and Drug Response

The VCaP xenograft model is widely used to evaluate the efficacy of androgen receptor-targeted therapies, including androgen deprivation therapy (ADT) and second-generation anti-androgens such as enzalutamide and abiraterone. Given the model’s AR-dependent growth, it is particularly valuable for testing the effects of AR signaling inhibitors and therapies that aim to block androgen receptor activation in castration-resistant prostate cancer (CRPC). VCaP xenografts are also used to study the mechanisms of resistance to androgen receptor-targeted therapies, making them ideal for evaluating combination therapies designed to overcome therapy resistance.

In addition to AR-targeted therapies, the VCaP xenograft model is used to evaluate novel therapies targeting the PI3K/AKT pathway, which is frequently dysregulated in prostate cancer and contributes to therapeutic resistance. The model is also valuable for studying the role of the tumor microenvironment in prostate cancer progression and metastasis, as well as for evaluating immunotherapies such as immune checkpoint inhibitors that may enhance anti-tumor immune responses. The model’s ability to replicate both primary tumor growth and metastasis to distant organs makes it an essential tool for evaluating the effects of treatments on tumor dissemination and survival.

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To request the VCaP 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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