TY - JOUR
T1 - Selective expression of stromal-derived factor-1 in the capillary vascular endothelium plays a role in Kaposi sarcoma pathogenesis
AU - Yao, Lei
AU - Salvucci, Ombretta
AU - Cardones, Adela R.
AU - Hwang, Samuel T
AU - Aoki, Yoshiyasu
AU - De La Luz Sierra, Maria
AU - Sajewicz, Agatha
AU - Pittaluga, Stefania
AU - Yarchoan, Robert
AU - Tosato, Giovanna
PY - 2003/12/1
Y1 - 2003/12/1
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2003-02-0641
DO - 10.1182/blood-2003-02-0641
M3 - Article
C2 - 12907452
AN - SCOPUS:10744230540
VL - 102
SP - 3900
EP - 3905
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -