LC3-positive puncta increase in skeletal muscle of patient-derived xenograft mice

Abstract

Loss of muscle tissues in cancer cachexia has been partly attributed to the activation of autophagy; however, because the experimental animal models involved only canonical cell lines, this conclusion cannot be confirmed until it is evaluated for different pathological conditions. Hence, in the present study, we histologically examined the punctate signal for LC3, an autophagosome marker, in patient-derived xenograft (PDX) mice. When 10 PDX mice grafted with colorectal cancer tissues were examined, their body weight, muscle (gastrocnemius) weight, and area of muscle fiber were all significantly lesser than those of control mice. In addition, immunofluorescence microscopy revealed that the number of LC3-positive puncta per muscle fiber or fiber area was significantly higher in the PDX mice than in control mice. These results indicate that the autophagy-lysosomal degradation system is involved in cancer cachexia-induced muscle wasting, and that PDX mice are a useful model for pathological analyses of cachexic muscle loss.