Nutritional stress alone can control in vitro tumor formation and its invasive nature

The metastatic nature is an inherent property of the tumor. However, the effect of the environmental stress conditions on tumor microcosm in the context of metastasis needs to be analyzed. This work is proposed to analyze the tumor behavior under multiple metabolic stress conditions, such as deprivation of glucose, protein, and oxygen. The spheroid proliferation rate is observed to be influenced profoundly by the stress level where minimal stress produces compact spheroid and severe stress makes unstable aggregate like structures. It is observed that the non-invasive cancer cells cannot form spheroids under extreme stress. Stress conditions influence the mRNA levels of hypoxic, angiogenic and ECM deformation specific gene clusters. Spheroid reversal assay reveals the quiescent nature of the stressed spheroids under continuous stress conditions. However, after the rescue, the stressed spheroids were found to opt for different migration modalities. Extremely stressed non-invasive spheroids display atypical sprout-like growth within the invasion matrix and severely stressed spheroids can control the migration pattern of mesenchymal stem cells. Thus, it is concluded that multiple nutritional stress influences the spheroid formation and physiology along with the conversion of a non-invasive spheroid into quasi-invasive one.