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Gene-expression profile of triple negative breast cancer cells stimulated with post-surgery wound-healing fluids

ABSTRACT: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype showing high recurrences and mortality rate, for which no therapies besides chemotherapy are available to date. Lacking specific markers for an effective targeted therapy, TNBCs still represent the most important challenge for clinical oncologists.TNBC definition for lack of expression markers underscored the urgent need of discover the “drivers” for this disease and their role in aggressiveness to develop specific targeted therapies. In the effort to identify drivers responsible of early TNBC relapse, we choose to take advantage of the pro-tumorigenic activity of post-surgery wound healing fluids (WHFs) of breast cancer patients that represents the microenvironment constituted of peripheral blood of patients in which disseminated tumor cells reside and that can strongly influence the survival of tumor cells allowing distant relapses. . The stimulus of this enriched microenvironment created immediately post-surgery can determine a selecting pressure for the survival of most aggressive tumor cells modulating the expression of existing or new molecules on TNBC surface driving the develop of distant metastases. By using WHF to stimulate human TNBC cell models prior gene expression profile, we identify the significant up-modulation of the plasma membrane receptor CUB-domain containing protein 1 (CDCP1).

ORGANISM(S): Homo sapiens

PROVIDER: GSE59614 | GEO | 2017/06/12

SECONDARY ACCESSION(S): PRJNA255759

REPOSITORIES: GEO

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Project description:Despite recent advances, triple-negative breast cancer (TNBC) patients remain at high risk for recurrence and metastasis, which creates the need for innovative therapeutic approaches to improve patient outcomes. Cryoablation is a promising, less invasive alternative to surgical resection, capable of inducing tumor necrosis via freeze/thaw cycles. Necrotic cell death results in increased inflammatory signals and release of preserved tumor antigens, which have the potential to boost the local and systemic anti-tumor immune response. Thus, compared to surgery, cryoablation enhances the activation of T cells leading to an improved abscopal effect, defined as the occurrence of a systemic response after local treatment. We previously showed with a bilateral-tumor mouse model of TNBC that cryoablation of the primary tumor leads to increased infiltration of distant tumors by tumor infiltrating lymphocytes (TILs) and decreased rates of recurrence and metastasis. However, the early drivers of the cryoablation-generated abscopal effect are still unknown and knowledge of the mechanism could provide insight into improving the anti-tumor immune response through pharmacologic immune modulation in addition to cryoablation. Here we show that cryoablation of mouse mammary carcinomas results in smaller distant tumors that harbor increased frequencies of anti-tumor cells [such as natural killer (NK) cells], accompanied by a systemic increase in the frequency of migratory conventional type 1 dendritic cells (cDC1; CD103+ XCR1+), compared to resection. The changes in cell frequencies are mirrored by the immune gene signature of the distant tumors, with cryoablation inducing genes involved with NK cell activation and leukocyte-mediated toxicity, including IL11ra1 and Pfr1. These results better define the early mechanisms through which cryoablation improves tumor elimination, which is mediated by enhanced frequencies of anti-tumoral cells such as NK and cDC1s at the distant tumor and in the spleen of mice treated with cryoablation, respectively.

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Gene-expression profile of triple negative breast cancer cells stimulated with post-surgery wound-healing fluids

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