Pattern of Collagen Fibers and Localization of Matrix Metalloproteinase 2 and 9 during Breast Cancer Invasion

Abstract

Aims and Background

Parenchymal cells naturally interact, react and adapt with the environment including stromal components around them in order to maintain tissue architecture and function. However, studies have shown that this spontaneous interaction will become crucial in assisting cancer invasion. The purpose of the study was to analyze the pattern of collagen deposition and localization of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the tumor microenvironment during breast cancer invasion.

Methods and Study Design

A standard transmission electron microscopy procedure was used together with the immunogold technique with a few modifications.

Results

The ultrastructure of fibroblasts in the vicinity of cancer cells was thick, elongated and spindle shaped with nuclear indentations. Desmoplasia was present near the cancer cells. Collagen fibers were still arranged parallel to the cancer cells and fibroblasts but were less dense than collagen fibers far from cancer cells and fibroblasts. Collagen fibers were less dense in the pericellular region because of proteolytic enzyme activity, which facilitates the invasion of breast cancer cells. In immunogold localization analysis, matrix metalloproteinase 9 had consistent localization throughout cancer cells, fibroblast and stroma. In matrix metalloproteinase 2 localization, gold conjugates were more heavily deposited in cancer cells and fibroblasts than in the stroma.

Conclusions

Invasive breast carcinoma is not an independent entity, and its survival depends on the surrounding microenvironment.