Cancer cachexia is characterized by the wasting of skeletal muscle and adipose tissue, the mechanisms of which remain elusive. Cachexia is estimated to affect between 50 and 80% of cancer patients and accounts for over 20% of all cancer-related deaths. To investigate the development of this systemic condition, we consider two possible tumor-derived signaling methods for communication between the tumor and host tissues: microvesicles and soluble factors. Specifically, we focus on host tissue stem cells and the potential for recruitment and reprogramming that these tumor-derived signals may have. First we construct a mathematical model to examine the diffusion capabilities of the two signaling methods from a blood vessel into the tissue. A diffusion-consumption partial differential equation is proposed and under the quasi-static state, real analytic solutions are found and discussed. Next we construct a host-level mathematical framework using ordinary differential equations that incorporates the systemic signaling between the tumor and muscle/adipose tissues. Three hypothesized cachexic mechanisms are examined: (1) the tumor directly produces inhibitors of muscle/adipose mass, (2) the tumor actively recruits MSCs from these tissues reducing their regenerative potential, and (3) the tumor produces factors that sensitize the muscle/adipose tissues to inhibitors, increasing their effectiveness. Experimental data, involving bone marrow-derived and adipose tissue-derived mesenchymal stem cells, is analyzed and used to help parameterize these models. Together, our experimental data and model analyses suggest that the two different signaling mechanisms may act synergistically in the development of cachexia, and that the reprogramming of host tissue stem cells may be a significant contributor to the condition.