Higher metastatic efficiency of KRas G12V than KRas G13D in a colorectal cancer model

• DOI: 10.1096/fj.14-262303
• Publication Date: 2014-10-31T03:48:50Z
• Authors: Patricia Alamo; Alberto Gallardo; Federica Di Nicol...; Miguel Angel Pavón; Isolda Casanova; Manuel Trias; María Antonia Man...; Antonio Lopez‐Pousa; Antonio Villaverde; Esther Vázquez; Alberto Bardelli; María Virtudes Cé...; Ramón Mangues
• Keywords: Viral Oncogene

Although all KRas (protein that in humans is encoded by the gene) point mutants are considered to have a similar prognostic capacity, their transformation and tumorigenic capacities vary widely. We compared metastatic efficiency of G12V (Kirsten rat sarcoma viral oncogene homolog with valine mutation at codon 12) G13D aspartic 13) oncogenes an orthotopic colorectal cancer (CRC) model. Following subcutaneous preconditioning, recombinant clones SW48 CRC cell line [Kras wild-type (Kras WT)] expressing or allele were micro-injected mouse cecum. The percentage animals developing lymph node metastasis was higher than mice. Microscopic, macroscopic, visible lymphatic foci 1.5- 3.0-fold larger mice (P< 0.05). In lung, only microfoci developed both groups. primary tumors had lower apoptosis (7.0 ±1.2 vs. 7.4 ± 1.0 per field, P = 0.02), tumor budding invasion front (1.2 0.2 0.6 0.1, P= 0.04), C-X-C chemokine receptor type 4 (CXCR4)-overexpressing intravasated emboli (49.8 9.4% 12.8 4.4%, < 0.001) tumors. showed Akt activation, β5 integrin, vascular endothelial growth factor A (VEGFA), Serpine-1 overexpression, whereas integrin β1 angiopoietin 2 (Angpt2) overexpression. increased survival, invasion, intravasation, specific molecular regulation observed consistent aggressiveness patients (his oncogene.—Alamo, P., Gallardo, A., Di Nicolantonio, F., Pavón, M. Casanova, I., Trias, M., Mangues, Lopez-Pousa, Villaverde, Vázquez, E., Bardelli, Céspedes, V., R. Higher FASEB J. 29, 464-476 (2015). www.fasebj.org