Quantitative assessment of breast cancer liver metastasis expansion with patient-derived xenografts
| Autor: | Madhumitha Sriram, Michael O. Idowu, Patricija Zot, J. Chuck Harrell, Mohammad A. Alzubi, Tia H. Turner, Sahib S. Sohal |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty Neutrophils Mammary gland Transplantation Heterologous Breast Neoplasms Mice SCID Metastasis 03 medical and health sciences 0302 clinical medicine Breast cancer Surgical oncology Mice Inbred NOD Internal medicine Cell Line Tumor medicine Animals Humans Breast Hematology business.industry Macrophages Liver Neoplasms Cancer General Medicine medicine.disease Disease Models Animal 030104 developmental biology medicine.anatomical_structure Oncology Liver 030220 oncology & carcinogenesis Cancer cell Cancer research Immunohistochemistry Female business Neoplasm Transplantation |
| Zdroj: | Clinicalexperimental metastasis. 36(3) |
| ISSN: | 1573-7276 |
| Popis: | Advanced breast cancer often spreads to the bone, brain, liver, and lungs. The survival time of a patient with breast cancer liver metastasis is often less than 9 months without treatment. Experimental model systems often focus on the lung as a site of metastatic relapse, and therefore, there is less of an understanding of the biological processes that occur during expansive liver metastasis growth. In these studies, 14 genetically distinct breast cancer patient-derived xenografts (PDXs) were characterized for growth in the liver after portal vein injection of cancer cells. Growth in the liver occurred in 12 of 14 models, and the relative growth rate across the PDXs was overall similar to growth in the mammary gland. Pathological and immunohistochemical analyses revealed that the proliferation rates of metastases were relatively similar as the metastases expanded until the tumors became necrotic, and then slightly lower proliferation rates were observed. There were influxes of macrophages and neutrophils as the metastases increased in size, suggesting these innate immune cells may result in differential responses to therapeutics in micrometastases compared to macrometastases. The development and characterization of these models is important as future studies can utilize this information to determine if targeted therapies can slow the progression of metastatic disease at different stages in the liver. |
| Databáze: | OpenAIRE |
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