Fig 1.
In vivo selection of a PDX breast cancer-derived metastatic variant.
A. SCID mice were implanted in the mammary fat pad (mfp) with tumor fragments of the triple negative breast cancer PDX tumor HCI-002. B. Two months later, primary tumors were resected. C. After 7 months, one mouse developed on overt lung metastasis that was positive for the Human Leukocyte Antigen (HLA). D. Fragments of this lung metastasis were implanted in the mammary fat pads (mfp) of naive SCID mice and the variant called HCI-002 ML2 was isolated. This new variant grew with an accelerated rate when compared to the parental HCI-002 PDX. E. HCI-002 LM2 tumors were resected and mice kept alive. F. Seven months after primary tumor resection a spontaneous lung metastases was detected. G. Pieces of the metastatic nodule found in the lungs were implanted in the mfp of naive SCID mice, creating a new variant, called HCI-002 LM2-1.
Fig 2.
Acceleration of tumor growth of the variants derived from a metastasis.
Graph showing the tumor growth rate of consecutive passages of two different tumors and their variants derived from lung metastases and representative slides stained for H&E: A. HCI-001; B. HCI-001 LM1; C. HCI-002; and D. HCI-002 LM2. Tumors did not show an increase in their growth rate with successive passages. The variants derived from lung metastases have an accelerated growth when implanted orthotopically as primary tumors in the mfp compared to the parental tumors. Scale bars, 150 μm.
Fig 3.
Increase in the percentage of mouse-derived thymomas.
A. Table showing the numbers of metastases of human origin and the number of tumors of murine origin (mouse thymic lymphomas) found in all the tumor types. B. Gross morphology of a thymic lymphoma. The arrow shows a mouse thymoma. C. Histopathological sections of a thymic lymphoma of mouse origin stained with H&E, anti-HLA, anti-mouse CD34 and anti-mouse Ki67. These tumors (negative for HLA, with no human component) presented high rates of proliferation and were positive for the hematopoietic progenitor cell antigen CD34. Scale bars, 150 μm.