Molecular insights of metastasis and cancer progression derived using 3D cancer spheroid co-culture in vitro platform

Graphical abstract where the theme of the review is summarized. The figure illustrates the Tumor developed in the organ (Lung) flourishes at its growth site with the help of cancer associated stromal cells. The cancer cells gears up to metastatic mode and migrates to the favourable secondary site of growth (Bone). It follows all the steps involved in metastasis where host defence plays vital role in cancer cell survival and metastasis in circulation. In turn the tumor associated cells helps cancer cells to get metastatic characteristics by secreting various biomolecules such as growth factors, and exosomes carrying miRNA. [Display omitted] •3D spheroid co-culture in vitro technique is promising platform to study vital step of cancer metastasis leading to cancer progression.•The review provides postulated nomenclature for in vitro spheroids and their probable definitions.•3D spheroid co-culture allows to study the supportive/feedback loop of stromal and cancer cells in vitro mimicking the tumor microenvironment.•The patient-derived cancer cells spheroid co-cultured with the stromal cells in vitro help to formulate promising personalized treatment.•The review also highlights the biomaterials and biofabrication techniques used for developing the 3D spheroid co-culture platforms. The multistep metastasis process is carried out by the combinatorial effect of the stromal cells and the cancerous cells and plays vital role in the cancer progression. The scaffold/physical cues aided 3D cancer spheroid imitates the spatiotemporal organization and physiological properties of the tumor. Understanding the role of the key players in different stages of metastasis, the molecular cross-talk between the stromal cells and the cancer cells contributing in the advancement of the metastasis through 3D cancer spheroid co-culture in vitro platform is the center of discussion in the present review. This state-of-art in vitro platform utilized to study the cancer cell host defence and the role of exosomes in the cross talk leading to cancer progression has been critically examined here. 3D cancer spheroid co-culture technique is the promising next-generation in vitro approach for exploring potent treatments and personalized medicines to combat cancer metastasis leading to cancer progression.