Hematogenic Dissemination of Triple-negative Versus Hormonal Receptor-positive Breast Cancer Cells

In Vivo. 2015 Jul-Aug;29(4):435-44.

Abstract

The aim of this study was to characterize the hematogeneous spread, in vivo, of breast cancer (BC) cell lines that express hormonal receptors (HR) comparing with triple-negative (TN) BC, particularly considering the lung and liver. Female Balb/c nu nu mice (n=30) were injected with two breast cancer cell lines (MCF7 and HCC1806). Nuclear medicine imaging with Technetium ((99m)Tc)-hydroxymethylene diphosphonate ((99m)Tc-HMDP) and (99m)Tc-Hexakis 2-methoxy-2-methylpropylisonitrile (MIBI) were performed between the 7th and 8th weeks after injection. The histological metastatic foci were analyzed by morphometric and immunohistochemistry studies regarding estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (ERBB2) and cytokeratin (CK)-5/6. The mean area of lung metastasis in MCF7 cases was significantly higher (p=0.023), although the number of liver foci was higher in the HCC1806 group (p=0.006). Logistic regression revealed a potentiating model for liver metastasis with HCC1806 cells (odds ratio=16; p=0.03). The number and area of lung-metastatic foci were not predictive of liver dissemination. Lung metastasis study showed ER positivity in 57.1% of the MCF7 group, compared to 80% of the HCC1806 group. PR was positive in 42.9% of MCF7 cases and negative in 60% of HCC1806 cases. HR-positive cells developed massive lung metastization. TN cells seem to potentiate liver metastasis. ER, PR, ERBB2 and basal-like CK expression in metastases was not uniformly correlated with that of primary tumor cells.

Keywords: Breast cancer; animal model of dissemination; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / secondary
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / secondary
  • Mice
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / pathology*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Triple Negative Breast Neoplasms / diagnosis
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2