Intestinal smooth muscle aberrations in pancreatic cancer patients with sarcopenia

Abstract

Background

Cancer cachexia is characterized by impaired function of skeletal and cardiac muscle. Smooth muscle is abundantly present in the body and critical for the function of the gastrointestinal tract. Given the frequently reported gastrointestinal symptoms in cancer patients, we hypothesized that the smooth musculature could be compromised in cancer patients with sarcopenia.

Methods

Full-thickness jejunal tissue sections from 57 pancreatic cancer patients were analysed by picrosirius red stains and immunohistochemistry for α-smooth muscle actin (α-SMA), smoothelin, and CD117 (c-kit). Muscle wall thickness, contractile marker expression, and collagen deposition were quantified. Patients were assigned to a sarcopenia or non-sarcopenia group based on their skeletal muscle index.

Results

Intestinal smooth muscle wall thickness did not differ between the sarcopenia and non-sarcopenia group (1,661 ± 125.0 vs. 1,439 ± 93.5 μm, P = 0.41). Whereas α-SMA staining intensity was similar in both groups, staining intensity of smoothelin, a key marker of the contractile smooth muscle cell phenotype, was reduced (143.0 ± 22.6 vs. 125.4 ± 29.3 arbitrary units, P = 0.02) in sarcopenic patients. The distribution of CD117⁺ interstitial cells of Cajal was similar in both groups, but pronounced collagen deposition around the myenteric plexus was more often observed in patients with sarcopenia (P = 0.04).

Conclusions

These data suggest that cancer cachexia is not only associated with skeletal and cardiac muscle wasting, but also affects the intestinal smooth musculature. Reduced contractile smooth muscle marker expression and fibrosis around the myenteric plexus suggest that both contractile function of smooth muscle cells and regulation of their contractile functionality could be compromised.