Stromal cells in breast cancer as a potential therapeutic target

Abstract

Breast cancer in the United States is the second most commonly diagnosed cancer in women. About 1 in 8 women will develop invasive breast cancer over the course of her lifetime and breast cancer remains the second leading cause of cancer-related death. In pursuit of novel therapeutic strategies, researchers have examined the tumor microenvironment as a potential anti-cancer target. In addition to neoplastic cells, the tumor microenvironment is composed of several critical normal cell types, including fibroblasts, vascular and lymph endothelial cells, osteoclasts, adipocytes, and immune cells. These cells have important roles in healthy tissue stasis, which frequently are altered in tumors. Indeed, tumor-associated stromal cells often contribute to tumorigenesis, tumor progression, and metastasis. Consequently, these host cells may serve as a possible target in anti-tumor and anti-metastatic therapeutic strategies. Targeting the tumor associated host cells offers the benefit that such cells do not mutate and develop resistance in response to treatment, a major cause of failure in cancer therapeutics targeting neoplastic cells. This review discusses the role of host cells in the tumor microenvironment during tumorigenesis, progression, and metastasis, and provides an overview of recent developments in targeting these cell populations to enhance cancer therapy efficacy.

Macrophage HIF‐2α regulates tumor‐suppressive Spint1 in the tumor microenvironment

“…In contrast, pro‐HGF within the tumor microenvironment likely stems from other sources than tumor cells and macrophages. While there is abundant evidence that cancer‐associated fibroblasts are a major source of pro‐HGF in breast carcinomas, adipocytes derived from monocyte/macrophage progenitors were recently shown to provide HGF to enhance migration of tumor cells when coinjected subcutaneously with E0771 cells into mice…”

“…In contrast, pro-HGF within the tumor microenvironment likely stems from other sources than tumor cells and macrophages. While there is abundant evidence that cancer-associated fibroblasts are a major source of pro-HGF in breast carcinomas, 46,[56][57][58] adipocytes derived from monocyte/macrophage progenitors were recently shown to provide HGF to enhance migration of tumor cells when coinjected subcutaneously with E0771 cells into mice. 59 Interestingly, while we found many genes to be differentially expressed between wt and HIF-2α knockout TAMs, only roughly a third showed reduced expression in HIF-2α-deficient macrophages, indicative for a potential direct transcriptional regulation.…”

Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment

“…The adaptive immune response is more specific than the innate immune response and can be antibody-mediated or cell-mediated, with Tand B-cells as the key cell types driving this response [12]. T-cells are a type of lymphocyte that matures in the thymus, with several different subtypes that play a distinct function in immune response [13]. Cytotoxic T-cells kill cancer cells [13], T-helper cells assist other cell types during the The cellular components of the TME can vary in different regions of the tumor [5], as well as between patients and even between tumors in a single patient [6].…”

“…T-cells are a type of lymphocyte that matures in the thymus, with several different subtypes that play a distinct function in immune response [13]. Cytotoxic T-cells kill cancer cells [13], T-helper cells assist other cell types during the The cellular components of the TME can vary in different regions of the tumor [5], as well as between patients and even between tumors in a single patient [6]. Each of these cellular components has its own behavior in terms of migration, proliferation, differentiation, apoptosis, adhesion, and response to treatment.…”

“…T-cells are a type of lymphocyte that matures in the thymus, with several different subtypes that play a distinct function in immune response [13]. Cytotoxic T-cells kill cancer cells [13], T-helper cells assist other cell types during the immune response, and T-regulatory cells (Treg) play an important role in immunological tolerance. In the case of cancer, in addition to normal antigens (self), cancer cells express antigens unique to the tumor, which can result in an immune response.…”