Cancer Stem Cell Research: Current Situation and Problems

Abstract

The concept of a "cancer stem cell system" that continues to supply cancer component cells has been proposed. It is time to apply stem cell studies, which is a field of expertise in regenerative medicine, to cancer treatment. Cancer treatments that effectively attack cancer stem cells acting as a manufacturing plant for producing differentiated cancer progenies will be designed by revealing the cancer stem cell system. Therefore, in the near future we hope that revolution will occur in cancer therapy to eradicate cancer and prevent the recurrence thereof. In this review we discuss the current situation and problems of cancer stem cell research.

Preliminary screening and identification of stem cell-like sphere clones in a gallbladder cancer cell line GBC-SD

“…However, it has been demonstrated that they be isolated by several ways including surface marker sorting (Al-Hajj et al, 2003;Singh et al, 2004), side-population cells selecting (Hadnagy et al, 2006;Moserle et al, 2010), and mammosphere cultures (Ponti et al, 2005;Yu et al, 2008). Most CSCs form clones when nurtured in low adhesive vessels (Chumsri and Burger, 2008;Kobayashi et al, 2008;Gilbert and Ross, 2009), and further generate sphere clones in the present of growth factors such as epidermal growth factor (EGF). Therefore the sphere clone formation assay has been widely used for the separation and identification of CSCs (Ponti et al, 2005;Yu et al, 2008).…”

Stem cell therapy for hereditary breast cancer

“…injection or subcutaneous admin istration of a specific number of stem cells directly into therapeutically targeted areas. In addition, the high plasticity and migratory potential of BM stem cells also offer the possibility of mobilizing them in vivo or injecting these stem cell types in circulation to regenerate the particular functional progenitors for the tissue regeneration [15] [13]. However, molecular targeting of tumori genic cascade elements in tissue specific cancer progenitor cells, which are derived from the malig nant transformation of adult stem cells, also repre sents a novel approach for the treatment of diverse metastatic and incurable cancer types by combina tion therapies [14].…”

“…Since the metastatic spread of diverse tumor cells, including those from glioblastomas, melano mas, and pancreas, breast, and prostate cancers to other specific tissues/organs, such as lymph nodes, bone, lungs, and/or liver, appears to be governed by the expression of diverse angiogenic factors, such as VEGF VEGFR system, matrix metallo proteinases, urokinase type plasminogen activator (uPA), cyclooxygenase 2 (COX 2), chemokines, and surface adhesion molecules, their molecular targeting may also constitute another adjuvant can cer therapy [15]. In this matter, the specific block ade of the SDF 1 CXCR4 axis by using a specific anti SDF 1 antibody, anti CXCR4 antibody, or CXCR4 antagonist (TC14012, TN14003, or AMD3100) has notably been observed to prevent the metastatic spread and interfere with the hom ing of breast and prostate cancer epithelial cells at their target metastatic sites, including lymph nodes, bone, and lungs [16].…”

“…The simultaneous inhi bition of diverse hormone and growth factor sig naling pathways, including BRCA1, ER, AR, IGFR, EGFR, hedgehog, Wnt/β catenin, Notch, and/or G protein coupled receptors, as well as VEGFR and PDGFR cascades, which can act in cooperation by stimulating the growth, invasion, and metastatic spread of cancer cells at distant sites during the different stages of cancer progression, may also constitute more effective therapiesagainst the aggressive and highly metastatic cancer forms [15,16]. As a matter of fact, some works have revealed that complex cross talks may occur among the AR, ER α/ER β, EGFR/ErbB2 sig naling cascades in breast cancers [17,18].…”

“…Among them, the molec ular targeting of distinct oncogenic signaling ele ments, which are activated in the cancer cells dur ing the progression of numerous cancer, represents a promising strategy for the development of new chemopreventive treatments and combination ther apies against some aggressive and metastatic can cers. Inactivation and/or activition of diverse hor mones, growth factors, cytokines and chemokines (androgens, estrogens, EGF and TGF α/EGFR, IGF/IGFR, SHH/SMO, Wnt/β catenin, Notch, TGF β, and SDF 1/CXCR4), and tumorigenic signaling elements (telomerase, phosphatidylinosi tol 3 kinase [PI3K]/Akt, NF κB, and Myc 1) may contribute to the sustained growth and survival of stem cells, as well as their malignant transforma tion during the initiation and cancer progression [15,16]. Therefore, their molecular targeting is of importance to the elimination of cancer progenitor cells, thereby inducing a complete tumor regres sion and cancer remission.…”