review · Cancers
The tumour microenvironment plays an essential role in tumour initiation, development, growth, and maintenance. This microenvironment consists of extracellular matrix alongside various stromal cells, including cancer-associated fibroblasts, tumour endothelial cells, tumour-associated adipocytes, and tumour-associated macrophages. While the functions of these supporting cells are largely documented, their biological origin remains unclear, with competing theories pointing to surrounding healthy tissues or cancer cells. Recent findings suggest cancer stem cells possess differentiation abilities that generate these diverse cell lineages, thereby contributing to tumour heterogeneity and metastasis. Exploring this process through induced pluripotent stem cells supports the hypothesis that cancer stem cells may serve as a primary source for several tumour microenvironment cell types. Understanding these differentiation pathways and cellular interactions provides fresh perspectives on tumour architecture and points towards new considerations for cancer therapies.
Understanding how tumours construct their supportive surroundings is vital for deciphering why cancers spread and resist treatment. Identifying cancer stem cells as a potential origin for diverse stromal components explains the vast cellular diversity found within tumours. This conceptual shift offers researchers clearer directions for unravelling tumour architecture and designing therapeutic approaches that disrupt the microenvironment sustaining cancer development.
The abstract outlines early-stage conceptual research examining cellular origins in the tumour microenvironment using induced pluripotent stem cell models. While this biological framework could eventually guide oncology drug discovery teams in identifying therapeutic targets within the tumour niche, the work remains at a fundamental research stage. The abstract does not indicate a direct application pathway or near-term commercial development.
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The tumor microenvironment (TME) has an essential role in tumor initiation and development. Tumor cells are considered to actively create their microenvironment during tumorigenesis and tumor development. The TME contains multiple types of stromal cells, cancer-associated fibroblasts (CAFs), Tumor endothelial cells (TECs), tumor-associated adipocytes (TAAs), tumor-associated macrophages (TAMs) and others. These cells work together and with the extracellular matrix (ECM) and many other factors to coordinately contribute to tumor growth and maintenance. Although the types and functions of TME cells are well understood, the origin of these cells is still obscure. Many scientists have tried to demonstrate the origin of these cells. Some researchers postulated that TME cells originated from surrounding normal tissues, and others demonstrated that the origin is cancer cells. Recent evidence demonstrates that cancer stem cells (CSCs) have differentiation abilities to generate the original lineage cells for promoting tumor growth and metastasis. The differentiation of CSCs into tumor stromal cells provides a new dimension that explains tumor heterogeneity. Using induced pluripotent stem cells (iPSCs), our group postulates that CSCs could be one of the key sources of CAFs, TECs, TAAs, and TAMs as well as the descendants, which support the self-renewal potential of the cells and exhibit heterogeneity. In this review, we summarize TME components, their interactions within the TME and their insight into cancer therapy. Especially, we focus on the TME cells and their possible origin and also discuss the multi-lineage differentiation potentials of CSCs exploiting iPSCs to create a society of cells in cancer tissues including TME.
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DOI: 10.3390/cancers12040879
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