Cancer and stem cells

Abstract

Being the second leading cause of death globally, cancer has been a long-standing and rapidly evolving focus of biomedical research and practice in the world. A tremendous effort has been made to understand the origin of cancer cells, the formation of cancerous tissues, and the mechanism by which they spread and relapse, but the disease still remains mysterious. Here, we made an attempt to scrutinize evidences that indicate the role of stem cells in tumorigenesis and metastasis, and cancer relapse. We also looked into the influence of cancers on stem cells, which in turn represent a major constituent of tumor microenvironment. Based on current understandings of the properties of (cancer) stem cells and their relation to cancers, we can foresee that novel therapeutic approaches would become the next wave of cancer treatment.

Keywords: Cancer; cancer stem cells; metastasis; stem cells; tumor microenvironment; tumorigenesis.

Figure 1.

Possible cell origins of cancer. (a) In a clonal evolution concept, stepwise acquisition of mutations may transform cells to be CSCs, which have tumor initiating potential; (b) The intracellular bacteria may take up the host’s DNAs and then develop into cancer cells by hybridizing the acquired DNAs with their own ones and expressing the hybrid genomes; (c) Cancer in adults may develop from embryonal rudiments that are produced in excess and that remain in the tissues of the fully mature organs; (d) Cancer may arise in a cell that has the potential to divide and not be lost during normal tissue turnover; (e) Factors such as chemicals or viruses may induce dedifferentiation of mature adult cells to cause cancer; (f) Stem cells with gene mutations may acquire malignant phenotype and lead to cancer; (g) Progenitor cells may undergo transformation and become cancer cells. (A color version of this figure is available in the online journal.)

Figure 2.

Possible ways of cancer metastasis. (a) Primary tumor cells may translocate from the primary tumor to a distant organ and colonize within that organ; (b) CSCs within the population of CTCs may be the actual cells that form metastases; (c) Cells within TME may become induced CSCs as a consequence of EMT and lead to cancer metastasis; (d) Metastatic cancer cells may arise from cells of myeloid origin or from hybrid cells following fusion between macrophages and non-metastatic cancer cells, which travel to the lymph nodes and form matastases. (A color version of this figure is available in the online journal.)

Figure 3.

TME and MSCs transformation by different tumor-derived factors. TME is composed of a heterogeneous population of cells, including tumor cells and nearby endogenous stromal cells recruited by the tumor. MSCs within TME could be transformed into myofibroblasts or TAFs, which in turn promote tumor growth. (A color version of this figure is available in the online journal.)

Figure 4.

Therapeutic strategies in cancer therapy. (a) Traditional cancer therapies including surgery, chemotherapy, and radiation therapy are commonly used in clinic to treat cancer; (b) With recognition of the immune system in protecting the body from threats such as cancer cells, immune therapy strategies are developed to be a potent type of cancer therapy; (c) Bone marrow transplantation is successfully used to treat patients with hematological cancers; (d) Stem cells are integrated with anticancer drugs/enzymes/genes/oncolytic virus for their targeted delivery to tumors and metastases; (e) Therapeutic strategies directed at CSCs may avoid recurrence of the disease and may lead to better treatments for cancer patients. (A color version of this figure is available in the online journal.)

Figure 5.

Possible mechanisms of cancer relapse. Due to the heterogeneity nature of CSCs, the therapeutic agents are not particularly specific, leading to the failure of the agents in eradicating CSCs. The residual CSCs are responsible for the recurrence of cancer. (A color version of this figure is available in the online journal.)