The stroma influence in breast cancer development

Abstract

Introduction: The complex process between cancer invasion and stroma response is still being elucidated, but is clear that cancer is a disease of more than just malignant cells. The tumor interstitial fluid has an important role in initiating the immune response. Determining the composition of tumor interstitial fluid can give us information about poor or good prognosis. Moreover, access to breast cancer’s stroma permits us to identify the substances that can be used in early detection and monitoring the disease activity. Our aim is to summarize the recent studies on peri-tumoral stroma and tumor interstitial fluid compared to normal mammary gland structure and use the results for early diagnosis, monitoring disease and maybe change the therapeutical targets.

Materials and Methods: The study represents a literature review and is based on state-of-theart information colected from 12 articles on breast cancer development from PubMed.

Results: In comparison to normal mammary gland structure, in the peri-tumoral stroma of breast cancer there are increased alpha smooth muscle actin, collagen IV, hyaluronan, fibroblast activated protein, myeloid-derived suppressor cells, cancer Associated adipose and a variety of host cells including macrophages and fibroblasts. Elevated expression of hyaluronan, tumor Associated macrophages, vascular endothelial growth factor-A, myeloid-derived suppressor cells- tell us about a poor prognosis. Numerous studies have demonstrated that inhibition of hyaluronan synthesis using 4-MU, tyrosine kinase inhibitor imatinib, aromatase inhibitor letrozole reduce breast cancer tumor cell proliferation and migration.

Conclusion: Current therapies target primarily the carcinoma cells, although many women have recurrent disease or/and develop metastases. This study demonstrates the importance of tumor microenvironment in mammary cancer development and the necessity to apply the treatment that will includes both the stroma and the cancer cells.