Deciphering the Cancer Puzzle: Cancer Stem Cells Being the Pivotal Piece

Review Article

J Stem Cell Res Transplant. 2017; 4(1): 1025.

Deciphering the Cancer Puzzle: Cancer Stem Cells Being the Pivotal Piece

Basak U#, Dutta A#, Dutta Chowdhury D, Bhattacharya A, Banerjee S, Khan P and Das T*

Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata, India #These authors contributed equally to this work

*Corresponding author: Tanya Das, Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata 700 054, India/p>

Received: October 13, 2016; Accepted: January 06, 2017; Published: January 09, 2017


Cancer is the most devastating concern of today’s world, being the highest cause of global mortality with millions of new detected cases. Despite thorough research and implementation of novel treatment strategies, the worldwide burden of cancer is steadily increasing. The tumor recurrence remains the most dreaded reason behind this vicious battle. Recently a small population of cells, adorned with the property of self-renewal, differentiation and capable of forming tumor in nude mice, was identified within the tumor mass. This subset of stemlike cells within the neoplastic tissue is designated as Cancer stem cells or tumor initiator cells. Extensive research has now indicated that the cancer stem cells are the major culprit behind tumor initiation, angiogenesis, invasion, metastasis, drug resistance and tumor relapse. In addition to differentiating into non stem tumor cells to drive tumor progression, evidences are being accumulated that they can even trans differentiate into non tumor cells of different lineages in order to support tumor maintenance and advancement. All these concepts back up the idea that cancer can be regarded as a ‘stem cell disease’ with cancer stem cells being the most potential therapeutic target. Moreover, the concept of tumor cell plasticity depicting the inter-conversion between the non-stem cancer cells into cancer stem cells and vice-versa opens a new era of cancer research and a huge possibility towards developing more successful treatment strategies.

Keywords: Cancer stem cells; Differentiation; Self-renewal; Dedifferentiation; Plasticity; Transdifferentiation


ABC: ATP Binding Cassette; BMP: Bone Morphogenetic Protein; bCSCs: breast CSCs; CAFs: Cancer Associated Fibroblasts; CSCs: Cancer Stem Cells; CNS: Central Nervous System; CTLA4: Cytotoxic T-Lymphocyte-Associated Antigen4; ECs: Endothelial Cells; ELCs: Endothelial Like Cells; EGF: Epidermal Growth Factor; EMT: Epithelial to Mesenchymal Transition; GBM: Glioblastoma Multiforme; GSCs: Glioma Stem Cells; iPSCs: Induced Pluripotent Stem Cells; IL: Interleukin; MMP: Matrix Metalloproteinase; NSCCs: Non-Stem Cancer Cells; PD1: Programmed Cell Death Protein 1; PD-L1: PD-ligand-1; TF: Transcription Factor; TGF: Transforming Growth Factor; TAMs: Tumor-Associated Macrophages; TANs: Tumor Associated Neutrophils; VEGF: Vascular Endothelial Growth Factor


Cancer figure amongst the most devastating causes of morbidity and mortality globally. According to the World Health Organization (WHO), approximately 8.2 million deaths occurred due to cancer in 2012 while 14 million new cases were detected during the same period [1] and the number of new cases is expected to increase by 70% over the next 2 decades. This depressing statistic may be due to high rate of cancer recurrence which does not permit the disease-free survival of the patients. Recent studies have designated cancer stem cells, which are responsible for the tumor initiation, maintenance and metastasis [2], as the sole contributors of the various factors and traits associated with tumor aggression, resistance and relapse [3-5]. According to the American Association of Cancer Research, a CSC has been defined as ‘a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor’ [6] (Figure 1). In fact, like normal Stem Cells (SCs), CSCs are able to sustain multi-lineage differentiation and self renewal properties. The CSC concept can find its origins way back in the 19th century when the German pathologist Rudolf Virchow postulated that cancers occur because of the aberrant activation of dormant embryonic cells in the adult tissue [7]. He further implied that cancer does not originate spontaneously but that cancer cells must arise from other living cells. However, it was only after another 100 years when Dick et al. [8] in 1994 isolated leukemia SCs that the first concrete evidence supporting the CSC hypothesis arose. They defined these stem-like cells as leukemia initiating cells capable of forming tumor in nude mice. Subsequently, brain CSCs were discovered in 2001 [9,10] following which CSCs have now been discovered in the tumors of various different tissues and organs like breast [11], lung [12,13], colon [14-16], pancreas [17,18] ovary [19] and in melanoma [20]. Studies are underway trying to identify and characterize CSCs in other tissues as well. Here, we review the role of CSCs in cancer development and therapy as the evidence in support of the hypothesis that cancer is a stem cell disease.