The purpose of this review is to provide an overview of the effect of (lymph)angiogenic cytokines on hematopoietic cells involved in acute myeloid leukemia (AML). Like angiogenesis, lymphangiogenesis occurs in pathophysiological conditions but not in healthy adults. AML is closely associated with the vasculature system, and the interplay between lymphangiogenic cytokines maintains leukemic blast survival in the bone marrow (BM). Once AML is induced, proangiogenic cytokines function as angiogenic or lymphangiogenic factors and affect hematopoietic cells, including BM-derived immune cells. Simultaneously, the representative cytokines, VEGFs and their receptors are expressed on AML blasts in vascular and osteoblast niches in both the BM and the peripheral circulation. After exposure to (lymph)angiogenic cytokines in leukemogenesis and infiltration, immune cell phenotypes and functions are affected. These dynamic behaviors in the BM reflect the clinical features of AML. In this review, we note the importance of lymphangiogenic factors and their receptors in hematopoietic cells in AML. Understanding the functional characterization of (lymph)angiogenic factors in the BM niche in AML will also be helpful in interrupting the engraftment of leukemic stem cells and for enhancing immune cell function by modulating the tumor microenvironment.
Animals ; Cytokines/*immunology ; Hematopoietic Stem Cells/immunology/*pathology ; Humans ; Immunity, Cellular ; Leukemia, Myeloid, Acute/immunology/*physiopathology ; *Lymphangiogenesis ; Lymphatic Vessels/immunology/*physiopathology ; Vascular Endothelial Growth Factor A/immunology

OBJECTIVETo investigate the distribution patterns and proliferative activity of lymphatic vessels in colorectal carcinomas (CRC) and their relationship with tumor metastasis and disease prognosis.

METHODSThe microlymphatic density (MLD) and microvascular density in tumoral and non-tumoral areas of 96 cases of CRC were evaluated by immunohistochemistry, using monoclonal antibodies for podoplanin and CD34 respectively. The Ki-67 expression of the lymphatic and blood vessels was detected by double-labeling immunohistochemistry. The relationship between MLD and clinicopathologic features and prognosis was analyzed.

RESULTSThe lymph vessels at central and superficia1 portions of CRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at the tumor borders had large and open lumina. The MLD at tumor borders (51.2 +/- 25.5) was significantly higher than that in normal colorectal mucosa (29.4 +/- 9.0) and other portions of CRC (P < 0.01). The Ki-67 labeling index of the lymphatic lining cells at tumor borders (0.23 +/- 0.17) was significantly higher than that in other portions of CRC (P < 0.05). The MLD significantly correlated with lymphatic involvement by tumor cells, regional lymph node metastasis and distant metastasis (P < 0.01). The 5-year survival rate was also significantly lower in patients with high MLD (P < 0.05).

CONCLUSIONSNeolymphatic vessels are commonly seen in CRC, especially at tumor borders. High MLD at tumor borders is associated with metastasis. The detection of MLD at tumor borders may thus be useful in predicting lymph node metastasis and prognosis in patients with CPC.

Adenocarcinoma ; immunology ; pathology ; physiopathology ; Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; immunology ; pathology ; physiopathology ; Endothelium, Vascular ; immunology ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen ; metabolism ; Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels ; pathology ; Male ; Middle Aged ; Prognosis ; Survival Rate