Cancer stem cells in colorectal cancer from pathogenesis to therapy: Controversies and perspectives

Table 1 Cell surface and intracellular molecules suggested as putative cancer stem cell markers in colorectal cancer and their most important features

Marker	Other name	Gene location1	Function	Ref.
CD133	Prominin-1, AC133	Chr 4 (p15.32)	Encoding of a pentaspan transmembrane glycoprotein which binds cholesterol in cholesterol-containing plasma membrane microdomains	[22]
CD44	PGP-1, HUTCH-1, GP90, EPICAN, CDW44, MIC4	Chr 11 (p13)	Cell adhesion molecule; involved in lymph node homing and lymphocyte activation	[55,56]
EpCAM	ESA, CD326, MK- 1, KSA, HEA125, BerEp4, 17-1A, GA733-2, KS1/4, EGP-2, EGP34, TROP-1	Chr 2 (p21)	Epithelial cell adhesion molecule	[70]
CD24	HSA	Chr 6 (q21)	Mucin-like cell adhesion molecule	[76]
CD29	Β1 Integrin	Chr 10 (p11.2)	Receptor for extracellular matrix proteins; involved in regulation of cell migration, proliferation, survival, differentiation and death	[82]
Lgr5	GPR49	Chr 12 (q22-q23)	Receptor for R-spondin proteins; marker for adult stem cells	[89,90]
CD166	ALCAM	Chr 3 (q13.1)	Cell adhesion molecule	[96]

¹From http://www.ncbi.nlm.nih.gov/gene.

Table 2 Prognostic value of CD133

Marker	Prognostic value	Ref.
CD133	Worse outcome and higher risk of metastasis	[32]
	Independent prognostic marker for overall survival	[33]
	Association with CSC resistance to 5FU-based chemotherapy in CRC	[34]
	Association with resistance to conventional radiotherapy in CRC	[35]
	Prediction of distant recurrences after chemoradiotherapy in colon cancer patients	[35]
	High tumorigenicity of CD133+ CRC cells compared to CD133- cells due to their interaction with CAFs by paracrine signaling axis of CXCR4-SDF1	[36]
	Risk factor for poor overall survival in stage II and III in colon cancer patients	[37]
	Relationship with K-Ras and B-Raf mutations in CRC patients	[38]

CSC: Cancer stem cell; CRC: Colorectal cancer.

Table 3 Prognostic value of CD44

Marker	Prognostic value	Ref.
CD44	Association of CD44 downregulation with a lower metastatic potential of CRC cells	[61]
	Association of CD44 downregulation with a higher metastatic and migratory potential of CRC cells	[62]
	Association with a reduced survival	[63]
	Correlation of CD44 loss with a higher tumor aggressiveness	[64]
	Relation with CRC cells proliferation but not with patients outcome	[65]
	Association with lymph node involvement and invasion depth	[66]
	Unfavorable prognostic factor for overall survival in advanced CRC	[66]
	Correlation of CD44 loss with advanced tumor stage, vascular invasion, lymph node involvement and infiltrating tumor border	[67]
	Association of CD44 loss in the lesion invasive front with adverse outcome of CRC patients	[67]

CRC: Colorectal cancer.