CD44 and EpCAM: Cancer-Initiating Cell Markers

Abstract

Embryonic stem cells are immortal, can self renew, and differentiate into all cells of the body. The adult organism maintains adult stem cells in regenerative organs that can differentiate into all cells of the respective organ. Virchow's hypothesis that cancer may arise from embryonic-like cells has received strong support, as it was demonstrated that tumors contain few cells, known as cancer stem or cancer-initiating cells (CIC), that account for primary and metastatic tumor growth. CIC are mostly defined by expression of CIC-markers that are associated and correlated with the potential of CIC to grow in xenogeneic mice. CIC marker profiles have been elaborated for many tumors, with several markers as CD24, CD44, CD133, CD166, EpCAM, and some integrins, being expressed by tumors of different histological type. Their function in promoting CIC maintenance and activity is largely unknown. The fate of stem cells, determined by their position, is minutely regulated by few adjacent cells creating a niche. CIC also require a niche, mostly for settlement and growth in distant organs. This so called pre-metastatic niche is initiated by the primary tumor before metastasizing cell arrival. How do CIC prepare the pre-metastatic niche? Cancer cells secrete a matrix that serves a cross-talk with surrounding tissues. Additionally, cancer cells can abundantly deliver exosomes, which function as long-distance intercellular communicators. Studies on a rat pancreatic adenocarcinoma support our hypothesis that tumor-derived matrix and exosomes are the main actors in forming the pre-metastatic niche with CIC markers being engaged in matrix preparation and/or exosome delivery.

Cantharidin and norcantharidin impair stemness of pancreatic cancer cells by repressing the β-catenin pathway and strengthen the cytotoxicity of gemcitabine and erlotinib

“…CD24 is a heavily glycosylated protein, which was originally described as heat stable B cell-associated antigen. It is thought to be able to facilitate metastasis of tumor cells through binding to P-selectin (30).…”

“…CD44 participates in cell survival and proliferation by harboring chemokines and growth factors, such as HGF (hepatocyte growth factor). CD44 also plays a role in angiogenesis and invasion via MMP (matrix metalloproteinase) binding (30). CD44 mediates matrix formation, which is crucial for the settlement and growth at a secondary site, whereas apoptosis resistance of CD44 + cells supports the efficacy of metastasis formation (33).…”

“…Through interaction with integrins such as VLA-4, CD44 is able to activate the MAPK (mitogen-activated protein kinase) pathway. Finally, integrin activation may lead to activation of WNT/β-catenin signaling pathway, which has been proven to be associated with maintaining stemness of CSCs (30,34). In human pancreatic cancer samples, CD44 expression was correlated with histologic grade and the patients with CD44 + tumors showed poor prognosis (23).…”

“…EPCAM is thought to support metastasis formation (30). Previous investigation reported that modulation of cadherin-mediated cell-cell interactions by EPCAM could be a possible functional involvement of this molecule in tumor progression (37).…”

Exosome platform for diagnosis and monitoring of traumatic brain injury

“…Exosomes provide stable conformational conditions for their protein content, conserve bioactivity of their proteins, improve bio-distribution and support an efficient interaction with target cells. The complexity of extracellular vesicle-associated bioactive macromolecules supports a critical role in generating the tumour microenvironment [48,49]. Exosomes can transfer specific proteins to target cells for the delivery of signalling pathways [50,51].…”