IL-1β, IL-8, and matrix metalloproteinases-1, -2, and -10 are enriched upon monocyte-breast cancer cell cocultivation in a matrigel-based three-dimensional system

Abstract

Breast cancer remains the first cancer-related cause of death in women worldwide, particularly in developing countries in which most cases are diagnosed in late stages. Although most cancer studies are based in the genetic or epigenetic changes of the tumor cells, immune cells within the tumor stroma often cooperate with cancer progression. Particularly, monocytes are attracted to the tumor primary site in which they are differentiated into tumor-associated macrophages that facilitate tumor cell invasion and metastasis. In this study, we used three-dimensional cultures to form acini-like structures to analyze the inflammatory secretion profile of tumor cells individually or in co-culture with monocytes. Breast cancer cell lines and primary isolates from eight Mexican patients with breast cancer were used. We found high levels of RANTES/CCL5, MCP1/CCL2, and G-CSF in the breast cancer individual cultures, supporting an important recruitment capacity of monocytes, but also of neutrophils. The co-cultures of the tumor cells and monocytes were significantly enriched with the potent pro-inflammatory cytokines interleukin (IL)-1β and IL-8, known to support malignant progression. We also found that the interaction of tumor cells with monocytes promoted high levels of matrix metalloproteinases (MMP)-1, MMP-2, and MMP-10. Our study supports that a key event for malignant progression is the recruitment of different immune cell populations, which help to sustain and enhance a chronic inflammatory microenvironment that highly favors tumor malignancy.