Selective expression of stromal-derived factor-1 in the capillary vascular endothelium plays a role in Kaposi sarcoma pathogenesis.
Kaposi sarcoma (KS), the most common neoplasm in patients with AIDS, typically presents with multiple skin lesions characterized by "spindle cells," the vast majority of which are infected with KSHV (Kaposi sarcoma herpes virus, also named HHV-8). In patients with AIDS, the presence of cell-associated KSHV DNA in blood is predictive of subsequent KS development, but the mechanisms by which circulating KSHV-infected cells contribute to AIDS-KS pathogenesis are unclear. Here, we show that the chemokine stromal-derived factor-1 (SDF-1), which is constitutively expressed by skin capillary endothelium and displayed on the endothelial cell surface in association with heparan sulfate, can trigger specific arrest of KSHV-infected cells under physiologic shear flow conditions. Moreover, in the presence of soluble SDF-1 gradients, SDF-1 expressed on the endothelial barrier can promote transendothelial migration of KSHV-infected cells. By triggering specific adhesion of circulating KSHV-infected cells and favoring their entry into the extravascular cutaneous space, endothelial cell-associated SDF-1 in cutaneous capillaries may dictate the preferential occurrence of KS in the skin.
Yao
Lei
L
Experimental Transplantation and Immunology Branch, CCR, National Cancer Institute, National Institutes of Health, Bldg 10, Rm 12N226, MSC 1907, Bethesda, MD 20892, USA.
Salvucci
Ombretta
O
Cardones
Adela R
AR
Hwang
Sam T
ST
Aoki
Yoshiyasu
Y
De La Luz Sierra
Maria
M
Sajewicz
Agatha
A
Pittaluga
Stefania
S
Yarchoan
Robert
R
Tosato
Giovanna
G
D017088:AIDS-Related Opportunistic Infections / Q000473:pathology; D001706:Biopsy; D002196:Capillaries / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000032:analysis / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D019288:Herpesvirus 8, Human; D006801:Humans; D010477:Perfusion; D019718:Receptors, CXCR4 / Q000032:analysis / Q000502:physiology; D012514:Sarcoma, Kaposi / Q000098:blood supply / Q000209:etiology* / Q000473:pathology*; D012878:Skin Neoplasms / Q000098:blood supply / Q000209:etiology / Q000473:pathology; D014471:Umbilical Veins / Q000166:cytology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4