Development of mouse models of malignant phyllodes tumors by transplantation of syngeneic mammary gland cells expressing mutant H‐Ras

Abstract

Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast with epithelial and stromal components, and surgical resection is the standard and only available treatment for malignant PTs. To provide a better understanding of these tumors, we developed mouse models that recapitulate the pathological and clinical properties of human malignant PTs. Mouse undifferentiated mammary gland cells were infected with a retrovirus encoding the human oncoprotein H-Ras G12V , and the infected cells were transplanted orthotopically into the mammary fat pads of syngeneic mice. The transplanted cells showed a high tumorigenic activity, with the resulting tumors manifesting pathological characteristics including stromal overgrowth similar to those of human malignant PTs. The tumors also showed high rates of both local recurrence and lung metastasis. Our models may prove useful for studies of the pathophysiology of malignant PTs as well as facilitate the development of new treatments.

Therapeutic and immunomodulatory potential of pazopanib in malignant phyllodes tumor

“…The choice of HRAS mutation is peculiar as the gene is not typically implicated in PT formation. Most importantly, the study did not provide data that the mouse model could reflect the therapeutic susceptibilities of human PT 18 . Comparatively, we managed to establish both patient-derived cell line and xenograft models representative of the malignant PT.…”

Lung Adenocarcinoma Mouse Models Based on Orthotopic Transplantation of Syngeneic Tumor-Initiating Cells Expressing EpCAM, SCA-1, and Ly6d

“…We have previously generated a series of syngeneic mouse models for many types of malignancy, including osteosarcoma [16], leukemia-lymphoma [17], glioblastoma [18], choriocarcinoma [19], phyllodes tumors [20], ovarian cancer [21], and biliary tract cancer [22]. In these models, tissue-specific stem or progenitor cells of adult mice are transformed into tumor-initiating cells by gene modifications, and transfer of the resulting cells to syngeneic mice leads to the formation of tumors that recapitulate the phenotype of corresponding human malignancies.…”