# The Role of Hemosiderin-Laden Macrophages (HLMs) in the Metastasis of Mammary Gland Cancers in Bitches

## TL;DR

This study explores how iron-containing immune cells may contribute to cancer spread in female dogs, linking their presence in tumors to increased cancer cell growth.

## Contribution

The study identifies a novel association between hemosiderin-laden macrophages and cancer metastasis in canine mammary tumors.

## Key findings

- Hemosiderin-laden macrophages were found in both tumors and lymph nodes of dogs with mammary cancer.
- The number of these macrophages correlated with tumor cell proliferation and metastasis.
- A positive relationship was observed between macrophage presence in tumors and their occurrence in regional lymph nodes.

## Abstract

Mammary gland cancer is one of the most common cancers in female dogs, and its spread to regional lymph nodes often worsens the prognosis. Cells of the immune system, called macrophages, are known to influence how cancers grow and spread. Some macrophages contain iron deposits and are known as hemosiderin-laden macrophages. In this study, we examined mammary tumors and regional lymph nodes from dogs with and without cancer spread. We observed that iron-containing macrophages were present both in tumors and in lymph nodes and that their numbers were related to how actively tumor cells were dividing. This study helps to improve understanding of the tumor environment in canine mammary cancer and highlights the possible involvement of iron-containing immune cells in this disease.

Mammary gland tumors are among the most common neoplasms in female dogs. Macrophages are believed to play an important role in tumor progression and metastasis. The aim of this study was to determine whether hemosiderin-laden macrophages (HLMs) may be involved in the development of metastatic lesions in regional lymph nodes. Forty-two cases of mammary gland cancers in female dogs and their regional lymph nodes were included in the analysis. The samples were divided into two groups based on the presence or absence of metastases. The sections were stained with hematoxylin and eosin (HE) and Prussian blue and were additionally subjected to immunohistochemical labeling using antibodies against pan-cytokeratin (Pan-CK) and Ki-67. In 20 cases, no metastatic changes were detected in the regional lymph node, whereas metastases were identified in 22 cases. A positive correlation was observed between the number of HLMs in the tumor stroma and the number of HLMs in the regional lymph node. Furthermore, a positive correlation was found between Ki-67 nuclear immunoreactivity in the mammary tumor and the number of HLMs present within its stroma. HLMs may represent a component of the tumor microenvironment that promotes cancer cell proliferation and potentially contributes to the propensity for metastasis formation in mammary tumors of female dogs.