Feline Mammary Cancer

Abstract

Feline mammary carcinoma (FMC) is similar to human breast cancer in the late age of onset, incidence, histopathologic features, biological behavior, and pattern of metastasis. Therefore, FMC has been proposed as a relevant model for aggressive human breast cancer. The goals of this study were to develop a nude mouse model of FMC tumor growth and metastasis and to measure the expression of genes responsible for lymphangiogenesis, angiogenesis, tumor progression, and lymph node metastasis in FMC tissues and cell lines. Two primary FMC tissues were injected subcutaneously, and 6 FMC cell lines were injected into 3 sites (subcutaneous, intratibial, and intracardiac) in nude mice. Tumors and metastases were monitored using bioluminescent imaging and characterized by gross necropsy, radiology, and histopathology. Molecular characterization of invasion and metastasis genes in FMC was conducted using quantitative real-time reverse transcription polymerase chain reaction in 6 primary FMC tissues, 2 subcutaneous FMC xenografts, and 6 FMC cell lines. The histologic appearance of the subcutaneous xenografts resembled the primary tumors. No metastasis was evident following subcutaneous injection of tumor tissues and cell lines, whereas lung, brain, liver, kidney, eye, and bone metastases were confirmed following intratibial and intracardiac injection of FMC cell lines. Finally, 15 genes were differentially expressed in the FMC tissues and cell lines. The highly expressed genes in all samples were PDGFA, PDGFB, PDGFC, FGF2, EGFR, ERBB2, ERBB3, VEGFD, VEGFR3, and MYOF. Three genes ( PDGFD, ANGPT2, and VEGFC) were confirmed to be of stromal origin. This investigation demonstrated the usefulness of nude mouse models of experimental FMC and identified molecular targets of FMC progression and metastasis.

Analysis of Copy-Number Variations and Feline Mammary Carcinoma Survival

“…MYL10, ACTB, RAC1, and MYLPF) involved in cell movement, actin cytoskeleton remodelling, and cellular proliferation and motion such as SBDS, ITGAM, PDGFA, and RAC1. Among them, RAC1 actively promotes cell motility in breast cancer cells 64,65 and PDGFA has been reported as highly expressed in FMCs and derived cell lines 66 . Furthermore, E3 1.1-34.5 Mb harboured SERPINE1; a gene encoding a cell adhesion protein involved in invasion and metastasis promotion in different human malignancies including HBCs [67][68][69] Analysis of common CNLs significantly correlated with reduced survival intervals.…”

Serum SDF-1 levels are a reliable diagnostic marker of feline mammary carcinoma, discriminating HER2-overexpressing tumors from other subtypes

“…Due to the similarities between human breast cancer and feline mammary carcinoma [ 6 – 10 ], new clinical studies on FMC may identify novel diagnostic markers and therapeutic targets that can probably be used in human patients. Recently, it was demonstrated that stroma cells of breast tumors synthesize the chemokine SDF-1, which via its cognate receptor (CXCR4) supports tumor growth through autocrine and paracrine mechanisms [ 14 , 19 , 24 , 41 , 47 ].…”

“…The feline mammary carcinoma (FMC) is very common in cat (12-40% of all neoplasms), showing overexpression of the HER2 protooncogene in 33%-60% of the cases [ 1 – 5 ]. Sharing phenotypic and genotypic similarities with human breast tumor [ 6 – 10 ], spontaneous FMCs can also be classified in the same subtypes (luminal A, luminal B, luminal B-like, epidermal growth factor receptor type II-positive and triple negative) [ 7 , 11 ], being considered a suitable model for breast cancer studies.…”

Development of a radiolabeled caninized anti-EGFR antibody for comparative oncology trials

“…Simultaneously, these clinical trials with dog patients suffering from spontaneously occurring tumors would provide insights for a possible translation of this approach back to human oncology, or to other species, like cats, that are also heavily affected by EGFR-overexpressing malignancies [ 29 ]. Also here, this novel theranostic approach could exploit imaging options in order to select patients more effectively.…”