The tumor microenvironment (TME) promotes
tumor growth and
metastasis. We previously established the color-coded EL4
lymphoma TME model with
red fluorescent protein (RFP) expressing EL4 implanted in transgenic C57BL/6
green fluorescent protein (GFP) mice. Color-coded imaging of the
lymphoma TME suggested an important role of stromal cells in
lymphoma progression and
metastasis. In the present study, we used color-coded imaging of RFP-
lymphoma cells and GFP stromal cells to identify yellow-fluorescent genetically recombinant cells appearing only during
metastasis. The EL4-RFP
lymphoma cells were injected subcutaneously in C57BL/6-GFP transgenic mice and formed subcutaneous
tumors 14 days after
cell transplantation. The subcutaneous
tumors were harvested and transplanted to the abdominal cavity of nude mice.
Metastases to the liver, perigastric lymph node,
ascites, bone marrow, and primary
tumor were imaged. In addition to EL4-RFP cells and GFP-host cells, genetically recombinant yellow-fluorescent cells, were observed only in the
ascites and bone marrow. These results indicate genetic exchange between the stromal and
cancer cells. Possible mechanisms of genetic exchange are discussed as well as its ramifications for
metastasis. J. Cell. Biochem. 118: 4216-4221, 2017. © 2017 Wiley Periodicals, Inc.