The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice

Although recent advances have enabled hematopoietic stem cells (HSCs) to be enriched to near purity, more information about their characteristics will improve our understanding of their development and stage-related functions. Here, using microarray technology, we identified endothelial cell-selective adhesion molecule (ESAM) as a novel marker for murine HSCs in fetal liver. Esam was expressed at high levels within a Rag1− c-kitHi Sca1+ HSC-enriched fraction, but sharply down-regulated with activation of the Rag1 locus, a valid marker for the most primitive lymphoid progenitors in E14.5 liver. The HSC-enriched fraction could be subdivided into 2 on the basis of ESAM levels. Among endothelial antigens on hematopoietic progenitors, ESAM expression showed intimate correlation with HSC activity. The ESAMHi population was highly enriched for multipotent myeloid-erythroid progenitors and primitive progenitors with lymphopoietic activity, and exclusively reconstituted long-term lymphohematopoiesis in lethally irradiated recipients. Tie2+ c-kit+ lymphohematopoietic cells in the E9.5–10.5 aorta-gonad-mesonephros region also expressed high levels of ESAM. Furthermore, ESAM was detected on primitive hematopoietic progenitors in adult bone marrow. Interestingly, ESAM expression in the HSC-enriched fraction was up-regulated in aged mice. We conclude that ESAM marks HSC in murine fetal liver and will facilitate studies of hematopoiesis throughout life.

Cyclooxygenase-2 Expression Determines Neoangiogenesis in Gallbladder Carcinomas

Neo-angiogenesis may have an important role in the poor prognosis of gallbladder carcinoma. An enhanced expression of COX-2 was found in precancerous lesions and in gallbladder carcinoma, likely to be involved in carcinogenesis as well as in angiogenesis. To study the relationships between the COX-2 expression and degree of vascularization, as well as to evaluate their role in the prognosis of patients with gallbladder carcinoma. 27 cases of gallbladder adenocarcinoma were included, classified grading I-III according the WHO classification. The COX-2 and endothelial antigen CD105 expressions were assessed immunohistochemically. COX-2 expression was evaluated according to the percentage and staining intensity of positive cells into "COX-2 positive" and "COX-2 negative" groups. In order to assess tumor microvessel density (MVD), CD105 positively stained microvessels were counted for each specimen in predominantly vascular areas (hot spots) at 200 x magnification. The MVD ranged from 9 to 46 microvessels/field. 15 tumors belonged to the hypervascular group (MVD > or = 25) and 12 to the hypovascular group. There were 16 (59.2%) COX-2 positive cases. There was difference in the degree of angiogenesis between COX-2 positive vs. COX-2 negative group: 11 (68.8%) out of 16 "COX-2 positive" tumors were hypervascular, in comparison with just 4 (36.4%) of "COX-2 negative" tumors. Our data show that the MVD corresponds to the COX-2 overexpression in gallbladder carcinomas. Augmented tumor neovascularization induced by COX-2 might be responsible for the poor prognosis in gallbladder carcinoma patients.