Lung Cancer Onset in Wild Type Mice Following Bone Marrow Reconstitution with kras(v12) Cells.
A role for bone-marrow-derived cells (BMDCs) in tissue repair and malignancy onset has been proposed, but their contribution is still debated. We tested the ability of BMDCs containing the inducible kras(V12) oncogene to initiate lung adenocarcinoma. For our experimental strategy, we reconstituted lethally irradiated wild type mice with BMDCs carrying inducible kras(V12) and subsequently induced oncogene expression by 4-OHT administration. Epithelial lung lesions, from adenoma to adenocarcinomas, appeared at successive time points. These results show that lung tumors were derived from donor BMDCs and indicate a direct involvement of bone marrow cells in the development of epithelial cancers.
European Institute of Oncology, Department of Experimental Oncology, Milan, Italy.
Elena
E
Belloni
European Institute of Oncology, Laboratory of Hematology-Oncology, Milan, Italy.
Ines
I
Martin Padura
European Institute of Oncology, Department of Experimental Oncology, Milan, Italy.
Elvira
E
Gerbino
European Institute of Oncology, Laboratory of Hematology-Oncology, Milan, Italy.
Stefania
S
Orecchioni
European Institute of Oncology, Department of Experimental Oncology, Milan, Italy.
Fulvia
F
Fusar Imperatore
European Institute of Oncology, Laboratory of Hematology-Oncology, Milan, Italy.
Paola
P
Marighetti
European Institute of Oncology, Molecular Medicine for Care Program, Milan Italy.
Giovanni
G
Bertalot
European Institute of Oncology, Department of Experimental Oncology, Milan, Italy.|Dipartimento di Scienze della salute, Università degli Studi di Milano, Milan, Italy.
Pier
P
Giuseppe Pelicci
European Institute of Oncology, Laboratory of Hematology-Oncology, Milan, Italy.
Francesco
F
Bertolini
D000818:Animals; D016026:Bone Marrow Transplantation; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008822:Mice, Transgenic; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)