Abstract

Canine inflammatory mammary cancer (IMC) shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as a natural model for human inflammatory breast cancer (IBC). The aim of this study was to characterize a new cell line from IMC (IPC-366) for the comparative study of both IMC and IBC. Tumors cells from a female dog with clinical IMC were collected. The cells were grown under adherent conditions. The growth, cytological, ultrastructural and immunohistochemical (IHC) characteristics of IPC-366 were evaluated. Ten female Balb/SCID mice were inoculated with IPC-366 cells to assess their tumorigenicity and metastatic potential. Chromosome aberration test and Karyotype revealed the presence of structural aberration, numerical and neutral rearrangements, demonstrating a chromosomal instability. Microscopic examination of tumor revealed an epithelial morphology with marked anysocytosis. Cytological and histological examination of smears and ultrathin sections by electron microscopy revealed that IPC-366 is formed by highly malignant large round or polygonal cells characterized by marked atypia and prominent nucleoli and frequent multinucleated cells. Some cells had cytoplasmic empty spaces covered by cytoplasmic membrane resembling capillary endothelial cells, a phenomenon that has been related to s vasculogenic mimicry. IHC characterization of IPC-366 was basal-like: epithelial cells (AE1/AE3+, CK14+, vimentin+, actin-, p63-, ER-, PR-, HER-2, E-cadherin, overexpressed COX-2 and high Ki-67 proliferation index (87.15 %). At 2 weeks after inoculating the IPC-366 cells, a tumor mass was found in 100 % of mice. At 4 weeks metastases in lung and lymph nodes were found. Xenograph tumors maintained the original IHC characteristics of the female dog tumor. In summary, the cell line IPC-366 is a fast growing malignant triple negative cell line model of inflammatory mammary carcinoma that can be used for the comparative study of both IMC and IBC.

Highlights

  • Inflammatory mammary cancer (IMC) is the most aggressive mammary neoplasia that affects female dogs [1, 2]

  • IPC-366 cells adhered to culture flaks presented epithelium-like morphology and characteristics (Fig. 2A)

  • IMC and inflammatory breast cancer (IBC) are a subtype of aggressive mammary cancer that affects female dogs and humans, respectively [1, 2, 26]

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Summary

Introduction

Inflammatory mammary cancer (IMC) is the most aggressive mammary neoplasia that affects female dogs [1, 2]. Its counterpart disease in humans is known as inflammatory breast cancer (IBC) and accounts for less than 6% of human breast cancer diagnoses with a poor survival in women [3, 4]. In both species, this type of cancer is highly angiogenic and angioinvasive [5,6,7,8]. More than 33 human breast cancer cell lines from primary tumors, metastatic tumors and pleural effusion have been established [10, 11, 13]. For performing studies on IBC, the cell lines availability are limited to SUM149, SUM 190 and MDA-IBC-3, FC-IBC02 [12, 14, 15]

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