Methionine aminopeptidase 2 over-expressed in cholangiocarcinoma: Potential for drug target

Figures & data

Figure 1.  Immunohistochemical staining patterns of MetAP2 in human bile duct epithelium. A: normal biliary cells with negative staining, 40×magnification; B: hyperplastic and dysplastic bile duct epithelia with moderate staining, 20×magnification; C: well differentiated tubular CCA, 20×magnification and D: lymph node with metastatic CCA, with strongly positive staining, 10×magnification.

Table I.  Pathological features of CCA patients and expressions of MetAP2 in primary tumor tissues.

	MetAP2 expression level
	n	negative-weak	Moderate-strong	p
Age (yrs)	82
•  ≤ 56	41	11	30	1.000
•  > 56	41	11	30
Gender	82
• Male	60	18	42	0.285
• Female	22	4	18
Macroscopic appearance	82
• Mass forming	53	14	39	0.909
• Invasive Intraductal papillary	29	8	21
Tumor stage	68
• I–III	7	3	4	0.757
• IVA	11	3	8
• IVB	50	15	35
Tumor grade	82
• Invasive Intraductal papillary	29	8	21	0.339
• Well-differentiated	32	6	26
• Moderately differentiated	13	4	9
• Poorly differentiated	8	4	4
Vascular invasion	69
• Present	42	12	30	0.925
• Absent	27	8	19
Lymphatic invasion	69
• Present	52	16	36	0.568
• Absent	17	4	13
Neural invasion	69
• Present	27	11	16	0.084
• Absent	42	9	33
Tumor size	37
•  ≤ 5 cm	7	2	5	0.809
•  > 5 cm	30	10	20

Table II.  Comparison of MetAP2 expressions in bile duct epithelia.

	MetAP2 expression level
	n	0	1 +	2 +	3 +	P
Invasive intraductal papillary CCA
Non-dysplastic bile ducts	23	8	15	0	0
Hyperplasia/dysplasia	19	1	2	11	5	0.001^a
Primary CCA	29	3	5	13	8	0.001^a
Metastatic CCA	4	0	0	0	4
Mass forming CCA
Non-dysplastic bile ducts	36	19	13	4	0
Hyperplasia/dysplasia	33	7	5	15	6	0.001^a
Primary CCA	53	7	7	27	12	0.001^a
Metastatic CCA	7	0	0	1	6

^a=significant different from the non-dysplastic bile duct.

Figure 2.  Effect of Fumagillin on cell proliferation in CCA cells. A: Various CCA cell lines were treated 0.25 and 5 µg/ml of fumagillin for 72 h. Number of cells was determined using SRB assay as described in Materials and Methods. One hundred percent corresponded to the optical density of the control. Results are mean±SD from triplicate assays; B: Expression of MetAP2 of each CCA cell lines were determined by immunoblotting with anti-MetAP2, β-actin was used as internal standard. The numbers represent the quantitative analysis of MetAP2/β-actin.