Category
Basic
Description
Endogenous retroviruses (ERVs) are integrated into human and murine genomes and are typically silent in healthy conditions. In cancerous tissues, ERVs are actively expressed and have been correlated with increased metastasis in murine models. Due to their tumor-associated expression, ERVs are being investigated as immunotherapeutic targets. In murine mammary tissues, mouse mammary tumor virus (MMTV) represents a relevant ERV, whereas its human homologue, human endogenous retrovirus-K (HERV-K), is associated with human breast cancer. We hypothesized that the mouse model can be used to study the immunological effects of human and mouse ERVs on cancer metastasis. In this study, BALB/c mice were inoculated with 4T1 murine mammary carcinoma cells orthotopically and treated with subcutaneous vaccines consisting of ERV-containing cell culture supernatant in Freund’s incomplete adjuvant. Tumor growth was measured, and pulmonary metastatic colonies were quantified upon sacrifice. Our results indicated that vaccination with the culture media of MMTV-secreting 4T1 cells reduced pulmonary metastasis. Knocking down MMTV alleviated the therapeutic effect of 4T1 cell culture media. On the other hand, culture media of HERV-K-secreting T47D human breast cancer cells exacerbated pulmonary metastasis of 4T1 tumors, and knockdown of HERV-K abrogated the pro-metastatic effect. Collectively, these findings support the use of the mouse model to analyze the immunological effect of murine and human ERVs on metastatic progression. Further studies aim to replicate these observations and determine how ERV-specific immune responses regulate metastasis.
Vaccines Containing Mouse and Human Endogenous Retroviruses Demonstrate Opposite Effects on Lung Metastasis in a Murine Mammary Cancer Model
Basic
Endogenous retroviruses (ERVs) are integrated into human and murine genomes and are typically silent in healthy conditions. In cancerous tissues, ERVs are actively expressed and have been correlated with increased metastasis in murine models. Due to their tumor-associated expression, ERVs are being investigated as immunotherapeutic targets. In murine mammary tissues, mouse mammary tumor virus (MMTV) represents a relevant ERV, whereas its human homologue, human endogenous retrovirus-K (HERV-K), is associated with human breast cancer. We hypothesized that the mouse model can be used to study the immunological effects of human and mouse ERVs on cancer metastasis. In this study, BALB/c mice were inoculated with 4T1 murine mammary carcinoma cells orthotopically and treated with subcutaneous vaccines consisting of ERV-containing cell culture supernatant in Freund’s incomplete adjuvant. Tumor growth was measured, and pulmonary metastatic colonies were quantified upon sacrifice. Our results indicated that vaccination with the culture media of MMTV-secreting 4T1 cells reduced pulmonary metastasis. Knocking down MMTV alleviated the therapeutic effect of 4T1 cell culture media. On the other hand, culture media of HERV-K-secreting T47D human breast cancer cells exacerbated pulmonary metastasis of 4T1 tumors, and knockdown of HERV-K abrogated the pro-metastatic effect. Collectively, these findings support the use of the mouse model to analyze the immunological effect of murine and human ERVs on metastatic progression. Further studies aim to replicate these observations and determine how ERV-specific immune responses regulate metastasis.
