Establishment and characterization of novel cancer cachexia-inducing cell line, Aku60GC, of scirrhous gastric cancer.

Abstract

Cancer cachexia is a pathological state characterized by severe weight loss, skeletal muscle depletion, and adipose tissue reduction. Cancer cachexia is observed in gastric cancer (GC) with a higher incidence over 80%. Approximately 80% patients with advanced GC including scirrhous gastric cancer (SGC), which has the worst prognosis among all GC, are affected with cachexia. The exact pathophysiology in SGC cancer cachexia remains elusive, and therapeutic approaches for the cancer cachexia have not been established. Patient-derived cancer cachexia models are promising for elucidating the underlying mechanisms of disease progression and developing novel treatments, none of which originate from SGC. Therefore, we established a novel cancer cachexia-inducing cell line, designated Aku60GC, through stepwise selection of a patient-derived SGC cell line, HSC-60. Subcutaneous implantation of the Aku60GC cells into nude mice resulted in weight loss, muscle atrophy, and adipose tissue depletion with high reproducibility, accompanied by elevation of the circulating cytokines IL-8 and IL-18. Compared to parental HSC-60 cells, Aku60GC cells exhibited additional genomic changes, such as AKT2 and CCNE1 gains, a somatic mutation of RUNX1, and accelerated growth. Thus, our results demonstrate that the Aku60GC cell line is a valuable resource for research on cancer cachexia in SGC.