Avoiding hepatic metastasis naturally: Lessons from the cotton top tamarin (Saguinus oedipus)

Table 1 Comparison of cancer genetics in the cotton top tamarin and human

Stage of neoplasia	Sporadic human CRC	Human IBD-associated CRC	CTT colitis-CRC
Normal-appearing mucosa	APC initiator	Inflammation leading to mutations listed below	No cell line mutations in APC exon 4 and 15[58]
Early adenoma/indefinite dysplasia	Aneuploidy, methylation, Sialyl Tn	Aneuploidy, methylation, Sialyl Tn, MSI	90%diploid; no methylation[59]
Early promotor	MSI; kRAS, COX-2	DCC	kRAS absent[60]
Intermediate adenoma/low-grade dysplasia	c-src	c-src	c-src ND
Intermediate promoter	DCC/DPC4	kRAS	DCC/DPC4 ND; kRAS absent[60]
Late promoter	p53	APC	p53 ND; as above for APC exon 4 and 15[58]

Adapted from Itzkowitz and Harpaz 2004[61]; and Mattar MC, Lough D, Pishvaian MJ, Charabaty A[62]. APC: Adenomatous polyposis coli gene; MSI: Microsatellite instability; DCC: Deleted in colon cancer; kRAS: V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; COX-2: Cyclooxygenase 2 gene; c-src: Rous sarcoma gene that encodes for usual C-terminal inhibitory phosphorylation site (tyrosine-527); DPC4: Deleted in pancreatic carcinoma, locus 4; p53: Protein 53 kilodaltons; ND: Not done.

Table 2 Representative somatic sequences from the PELPK region of carcinoembryonic antigen in humans, cotton top tamarin and common marmoset

HCEA-A1 PELPKPSISSNNSKPVEDKDAVAFTCEPETQDA

CTT-WT PELPKPSISSNNSKPVEDKDAGAFTCEPETQDA

CM-WT PELPKPSISSINSKPVEDKDAGAFTCEPETQDA

M1-A1 (CTT) PEVPKPSISSNNSKPGGDKDAGAFTWEPETQDA

M2-A1 (CTT) PEVSKPSISSNNSKPGGDKDAGAFTWEPETQDA

M3-A1 (CTT) PEVSKPSISSNNSKPVGDKDAGAFTWEPETQDA

M4-A1 (CTT) PEVSKPSISSNNSKPVGDKDAGAFTWEPETQDA

M5-A1 (CTT) PEVSKPYISSNNSNPVENKDAGAFTWEPETQDA

M6-A1 (CTT) PEVSKPFIFSNNSKPGGDKDAGAFTWEPETQDA

M8-A1 (CTT) PEVSKPFIFRNNSKPGGDKDAGAFTWEPGTQDA

M10-A1 (CTT) PELPKPFIFSNNFKPVEDKDAVAFTCEPETQDT

M14-A1 (CTT) PELPKPFIFSNNFKPVEDKDAVAFTCEPETQDA

M15-A1 (CTT) PELPKPFIFSNNFKPVEDKDAVAFTCEPETQDA

M16-A1 (CTT) PELPKPSILSNNSKPVEDKDAVAFTCEPETQDA

M17-A1 (CTT) PELPKPSIPSNNSNPVEDKDAVGLTCEPDTQNT

M19-A1 (CM) PELPKPSISSYNSKPVEDKDAGAFTCEPETQDA

M20-A1 (CM) PELPKPSISSYNSKPVEDKDAGAFTCEPETQDA

M21-A1 (CM) PELPKPFISSYNFKPVEDKDAGAFTCEPETQDA

M24-A1 (CM) PELPKPSIFSNNSKPVEDKDAVAFTCEPETQDA

M27-A1 (CM) PELPKPSISSNNSNPVEDKDAVAFTCEPETQDA

M31-A1 (CM) PEVSKPFIFSNNSKPVGDKDAGAFTCEPETQDA

M40-A1 (CM) PGVPKPFIFRINFKPVGDKDAGAFTCEPETQDA

Sequences changes from those of wild type (germ line) are shown in bold. Published with permission of Springer[8].

Table 3 Biological attributes of the fibulin family[51-53]

Attribute	Fibulin-1	Fibulin-2	Fibulin-3	Fibulin-4	Fibulin-5
Invasion of endothelium	Decrease	Increase	Decrease	Unknown	Decrease
Binding of tropoelastin	Moderate	High	low	Moderate	High
Effect on angiogenesis	Unknown	Unknown	Reduced	Unknown	Reduce
MMP/fibronectin change	Increase	Unknown	Reduced	Unknown	Reduced

Table 4 Summarization of our findings in this study

Parameter	CTT	CM	Human
PELPK Change	+ + + +	+ +	-
CEAR expression	±	±	+ + + +
CEA glycosylation	±	±	+ + + +
CEACAM1 expression	-	-	+ + + +
Fibulin-5 expression	+ + +	+ + +	+ +1

¹Human data have limited staining data; Modified from and published with permission of Springer[8]. CTT: Cotton top tamarin; CM: Common marmoset; CEA: Carcinoembryonic antigen.