A Role for Resistance Exercise in Cancer: Destruction of Circulating Tumor Cells in Contracting Muscle

Abstract

OBJECTIVEAt the Roswell Park Cancer Institute in the 1980s, Leonard Weiss explored why muscle tissue gets few cancer metastases, despite its large blood flow. (Weiss, L., 1992. Biomechanical interactions of cancer cells with the microvasculature Cancer Metastasis Rev, 11(3), pp.227–235). He found that circulating tumor cells were destroyed in contracting quadriceps muscles and cardiac tissue, and during maximal lung inspiration. He further showed that as cancer cells squeeze through the much smaller capillaries, they elongate to the maximum extension of the cell membrane and hypothesized that additional forces on the cancer cell wall caused cell rupture. We analyzed Weiss' published lung data during a maximal inspiration, and found this induces radial stress of 8.7 KpA on a 4.6 mm diameter lung capillary. In our study, mathematical models were applied to ultrasound generated architectural data of the contracting biceps muscle, to determine radial stress under different exercise conditions.METHODS12 healthy males age 20–30 were asked to flex the right elbow from 5° to 90°, with no load, and then with a 10 pound weight, in supine and standing. Longitudinal 2D B‐mode ultrasound was performed of the long head of the biceps brachii muscle at specific measured locations based upon its proximal portion at the intertubercular groove and distal region at the anterior elbow joint line. Muscle length and maximum diameter was recorded and the truncated cone of the muscle image was converted to a cylinder of the same maximum diameter and shorter length (to keep constant volume). Odegard's strain energy function for small and large deformations associated with the active and passive response of transversely isotropic skeletal muscle was used to determine longitudinal and radial strain and stress, Young's modulus, and stiffness.RESULTSWe found the radial stress during biceps contraction to be: 1) 46 ± 26 KpA with the elbow unloaded at 90°; 2) 42 ± 17 KpA with participant in supine, the elbow at 90° and a 10 pound load on the biceps; and 3) 48±24 KpA with the participant standing and the biceps loaded with 10 pounds. With the elbow in 5° flexion, the radial stress is much lower, (15 KpA), at both loads and in both supine and standing.CONCLUSIONSShortening of biceps muscle results in radial stress well above the level calculated to rupture circulating tumor cells in the lungs. Muscle capillaries have stiffening of their wall, so the high radial stress of a short length contraction may be necessary for tumor cell destruction in muscle tissue. Large muscle metastases are found in very few persons with common cancers – lung (2%), colon (1%), breast and prostate (<.5%). In contrast, extraocular muscles rarely contract to their shortest, and metastases are found here in 6% of persons with locally advanced or metastatic breast cancer, and in 12% of all persons dying of cancer. Normal resting cardiac output (CO) is 5 l/min, with a pulse of 80 and a blood volume of 5 liters. Resistance exercise sufficient to raise pulse rate 50% to 120 will raise CO similarly 50% to 7.5 liters/min, with 1/3 the cardiac output now going through the exercising muscle. Every minute of exercise thus leaves 2/3 blood volume unfiltered. After a short 7 minutes of this level of exercise, all but .677 or 0.02% of the blood volume will have passed through the exercising muscle. We suggest design of exercise for persons with cancer based on aspects of muscle and capillary architecture.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.