Metastatic breast cancer cells in lymph nodes increase nodal collagen density.

Asif Rizwan,Camille Bulte,Menglin Cheng,Balaji Krishnamachary,Anusha Kalaichelvan,Zaver M. Bhujwalla,Kristine Glunde,Lu Jiang

doi:10.1038/srep10002

Abstract

The most life-threatening aspect of breast cancer is the occurrence of metastatic disease. The tumor draining lymph nodes typically are the first sites of metastasis in breast cancer. Collagen I fibers and the extracellular matrix have been implicated in breast cancer to form avenues for metastasis. In this study, we have investigated extracellular matrix molecules such as collagen I fibers in the lymph nodes of mice bearing orthotopic human breast cancer xenografts. The lymph nodes in mice with metastatic MDA-MB-231 and SUM159 tumor xenografts and tumor xenografts grown from circulating tumor cell lines displayed an increased collagen I density compared to mice with no tumor and mice with non-metastatic T-47D and MCF-7 tumor xenografts. These results suggest that cancer cells that have metastasized to the lymph nodes can modify the extracellular matrix components of these lymph nodes. Clinically, collagen density in the lymph nodes may be a good marker for identifying lymph nodes that have been invaded by breast cancer cells.

Highlights

The most life-threatening aspect of breast cancer is the occurrence of metastatic disease
The lymph nodes in mice with metastatic MDA-MB-231 and SUM159 tumor xenografts and tumor xenografts grown from circulating tumor cell lines displayed an increased collagen I density compared to mice with no tumor and mice with non-metastatic T-47D and MCF-7 tumor xenografts
The lymph nodes from the metastatic MDA-MB-231 and SUM159 xenografted mice, as well as mice that were injected with MDA-MB-231 cells through the tail vein, or xenografted with MDAMB-231-derived circulating tumor cells (CTCs), contained cytokeratin, visualizing cancer cells that had metastasized to these lymph nodes

Summary

Introduction

The most life-threatening aspect of breast cancer is the occurrence of metastatic disease. The lymph nodes in mice with metastatic MDA-MB-231 and SUM159 tumor xenografts and tumor xenografts grown from circulating tumor cell lines displayed an increased collagen I density compared to mice with no tumor and mice with non-metastatic T-47D and MCF-7 tumor xenografts These results suggest that cancer cells that have metastasized to the lymph nodes can modify the extracellular matrix components of these lymph nodes. The first lymph nodes into which lymphatic fluid is drained from a primary breast tumor are the sentinel lymph nodes, and as a consequence, they are typically the first lymph nodes to contain cancer cells that have escaped from the primary tumor. Metastatic tumors can alter the organization of venous blood vessels and can increase the proliferation of endothelial cells within the sentinel lymph nodes[15]. An increased number of macrophages was observed in the draining lymph nodes of breast cancer patients, in which these macrophages were shown to phagocytose keratinic debris[20]

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Conclusion