Expression of endothelial cell-associated molecules in AML cells

• Published in: Leukemia Vol. 16; no. 1; pp. 112 - 119
• Main Authors: WATARAI, M, MIWA, H, KITA, K, NITTA, M, SHIKAMI, M, SUGAMURA, K, WAKABAYASHI, M, SATOH, A, TSUBOI, K, IMAMURA, A, MIHARA, H, KATOH, Y
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 2002; Nature Publishing Group
• Subjects: Acute Disease; Angiopoietin-1; Angiopoietin-2; Antigens, CD7 - analysis; Biological and medical sciences; Blood Cells - pathology; Bone Marrow Cells - pathology; CD18 Antigens - biosynthesis; CD18 Antigens - genetics; Cell Cycle; Cells, Cultured - metabolism; Endothelial Growth Factors - biosynthesis; Endothelial Growth Factors - genetics; Endothelium, Vascular - cytology; Gene Expression Regulation, Leukemic; Hematologic and hematopoietic diseases; Humans; Immunophenotyping; Integrin alphaXbeta2 - biosynthesis; Integrin alphaXbeta2 - genetics; Leukemia, Myeloid - genetics; Leukemia, Myeloid - metabolism; Leukemia, Myeloid - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphokines - biosynthesis; Lymphokines - genetics; Macrophage-1 Antigen - biosynthesis; Macrophage-1 Antigen - genetics; Medical sciences; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neovascularization, Pathologic - genetics; Protein Biosynthesis; Proteins - genetics; Proto-Oncogene Proteins; Receptor, TIE-2; Tumor Cells, Cultured - metabolism; Umbilical Veins - cytology; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Chromosomal aberration; Endothelial cell; Angiogenic factor; Cell cell interaction; Carcinogenesis; Angiogenesis; Abnormal chromosome C8; Integrin; Hematopoiesis; Established cell line; Genetics; Abnormal chromosome G21; Tumor cell; Hybrid gene; Biological receptor; Chromosome translocation; Human; Angiopoietin 1; Cytokine; Vascular endothelium growth factor; Cytogenetics; Abnormal chromosome; Angiopoietin 2; Growth factor; Acute myelocytic leukemia
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2402326

Recently, it has been clarified that interaction between hematopoietic cells and endothelial cells is important in normal hematopoiesis and leukemogenesis. In this study, we examined the relationship between AML cells and endothelial cells by analyzing the expression profile of angiogenic factors, angiopoietin-1 (Ang-1), Ang-2, Tie-2 (a receptor for angiopoietins) and vascular endothelial growth factor (VEGF). Our results demonstrated that CD7(+)AML expressed Ang-2 mRNA frequently and integrin-family adhesion molecules (CD11c and CD18) intensively, suggesting the close correlation with endothelial cells. On the other hand, in t(8;21) AML cells, expression of Ang-2 was infrequent and expression of integrin-family adhesion molecules (CD11b, CD11c and CD18) was weak, suggesting the sparse association with endothelial cells. As for CD7(+)AML cells, despite the frequent and intense expression of endothelial cell-associated molecules (such as Ang-2, CD11c and CD18), intensity of Tie-2 expression was quite low (P < 0.05). Ang-2 expressed in CD7(+)AML cells is not considered to act in an autocrine fashion, but to work on endothelial cells to "feed" leukemic cells. Although Ang-2 is recognized as a natural antagonist for Tie-2, our data presented here suggested the alternative role of Ang-2 in the relationship between endothelial cells and leukemia cells, at least in a subset of leukemia such as CD7(+)AML. These results were supported by the study using AML cell lines, KG-1 (CD7 negative) and its subline KG-1a (CD7 positive); KG-1 had mRNA expression profile of Ang-1(+)Ang-2(-)Tie-2(+), while KG-1a showed Ang-1(+)Ang-2(+)Tie-2(-). These difference in the expression profile of angiogenic factors between CD7(+)AML and t(8;21)AML may explain the characteristic morphological features of these leukemias (CD7(+)AML as blastic type and t(8;21)AML as differentiative type).