Abstract: Inflammation is considered a key factor in the initiation, promotion, angiogenesis, and spread of tumors, with cytokines significantly influencing both the progression and defense mechanisms in breast cancer. The precise mechanisms initiating breast cancer remain unclear, though multiple theories have been proposed. Cytokines, a class of inducible and secreted proteins vital for immune cell communication, fall into several families, including tumor necrosis factors (TNFs), interleukins (ILs), interferons (IFNs), and colony-stimulating factors (CSFs). The interplay between inflammation and cancer occurs via two distinct but interconnected pathways: the intrinsic pathway, influenced by genetic mutations driving tumor development, and the extrinsic pathway, activated by chronic inflammation, which contributes to cancer risk. A variety of cytokines influence the inflammatory tumor microenvironment. Cytokines such as IL-1, IL-6, IL-11, TGF-β, and oncostatin M are implicated in promoting COX-2 expression, which in turn enhances VEGF production in tumor cells. These molecules support cancer cell proliferation, invasion, and metastatic behavior, with pathways like NF-κB amplifying these processes. Notably, TGF-β transitions from acting as a tumor suppressor to a factor promoting metastasis. While TNF-α can encourage tumor cell growth and motility, its localized administration at high doses exhibits antiangiogenic and antitumor properties. CSF-1 is believed to facilitate the infiltration of macrophages into breast tumors. Cell lines derived from breast cancer often express both CSF-1 and its receptor (CSF-1R), sustaining cell proliferation in models like SKBR3 and MDAMB468 through the ERK1/2 pathway, which activates c-Jun and enhances the expression of c-Myc and cyclin D1. IL-19 and IL-20 have been shown to stimulate breast cancer cell migration in vitro. On the other hand, IL-10, a strongly anti-inflammatory cytokine, acts by suppressing gene expression and antigen presentation, thereby reducing immune responses. Targeted therapies that inhibit specific cytokine pathways-such as the IL-6/sIL-6R signaling axis-represent promising strategies for breast cancer treatment. Moreover, hypoxic conditions and inflammatory responses are essential for the formation of new blood vessels (neoangiogenesis). In this context, cancer nanomedicine provides innovative solutions for improving drug delivery and reducing systemic toxicity. Nanoparticles (NPs), used as delivery systems, can be loaded with anti-inflammatory agents to enhance therapeutic outcomes.
Lovenya et al. (Tue,) studied this question.