Behaviour of mesenchymal stem cells from bone marrow of untreated advanced breast and lung cancer patients without bone osteolytic metastasis

Abstract

Tumour cells can find in bone marrow (BM) a niche rich in growth factors and cytokines that promote their self-renewal, proliferation and survival. In turn, tumour cells affect the homeostasis of the BM and bone, as well as the balance among haematopoiesis, osteogenesis, osteoclastogenesis and bone-resorption. As a result, growth and survival factors normally sequestered in the bone matrix are released, favouring tumour development. Mesenchymal stem cells (MSCs) from BM can become tumour-associated fibroblasts, have immunosuppressive function, and facilitate metastasis by epithelial-to-mesenchymal transition. Moreover, MSCs generate osteoblasts and osteocytes and regulate osteoclastogenesis. Therefore, MSCs can play an important pro-tumorigenic role in the formation of a microenvironment that promotes BM and bone metastasis. In this study we showed that BM MSCs from untreated advanced breast and lung cancer patients, without bone metastasis, had low osteogenic and adipogenic differentiation capacity compared to that of healthy volunteers. In contrast, chondrogenic differentiation was increased. Moreover, MSCs from patients had lower expression of CD146. Finally, our data showed higher levels of Dkk-1 in peripheral blood plasma from patients compared with healthy volunteers. Because no patient had any bone disorder by the time of the study we propose that the primary tumour altered the plasticity of MSCs. As over 70 % of advanced breast cancer patients and 30-40 % of lung cancer patients will develop osteolytic bone metastasis for which there is no total cure, our findings could possibly be used as predictive tools indicating the first signs of future bone disease. In addition, as the MSCs present in the BM of these patients may not be able to regenerate bone after the tumour cells invasion into BM/bone, it is possible that they promote the cycle between tumour cell growth and bone destruction.

The Roles of Epithelial-to-Mesenchymal Transition (EMT) and Mesenchymal-to-Epithelial Transition (MET) in Breast Cancer Bone Metastasis: Potential Targets for Prevention and Treatment

“…Bone is a dynamic tissue that is constantly remodeled through the resorption of old bone by osteoclasts and the subsequent formation of new bone by osteoblasts [46,47]. …”

The Effects of Astragalus Polysaccharide on Bone Marrow-Derived Mesenchymal Stem Cell Proliferation and Morphology Induced by A549 Lung Cancer Cells

“…Also, MSCs from cancer tissue of lung cancer patients have been shown to accelerate growth kinetics, and reduce sensitivity to cisplatin [30]. MSCs from the bone marrow of lung cancer patients without bone metastasis have shown a low capacity for adipogenic and osteogenic differentiation and increased chondrogenic differentiation [31]. However, the role of the interaction between lung cancer cells and MSCs remains poorly understood.…”

Mesenchymal Stromal Cell-Derived Extracellular Vesicles as Biological Carriers for Drug Delivery in Cancer Therapy

“…Despite several methods are available in the literature for viral inactivation –including solvents, detergents, irradiation, and nanofiltration-, their utilization may alter EVs structure and content ( Burnouf et al, 2019 ). Regarding MSCs tissue source, as many studies suggest, MSCs isolated from cancer patients may exert some pathological alterations, so the obtaining of healthy volunteers-derived allogeneic MSCs for EVs isolation is highly recommended ( Hofer et al, 2010 ; Fernandez Vallone et al, 2013 ; Rühle et al, 2019 ). Open/semi-open systems have been the most utilized for cell culturing, although they may be associated with variability between batches, risk of contamination, and lack of real-time process control ( Roura et al, 2017 ).…”