Malignant B cells from patients with primary central nervous system lymphoma express stromal cell-derived factor-1.
Although the pathogenesis of primary central nervous system lymphoma (PCNSL) remains unclear, it is hypothesized that specific chemokine-chemokine receptor interactions may attract malignant B lymphocytes into the CNS. Formalin-fixed, paraffin-embedded brain biopsy specimens from 40 patients with PCNSL were immunostained by an indirect immunohistochemical method incorporating antigen retrieval to detect the presence of B-cell chemokines, stromal cell-derived factor-1 (SDF-1; CXCL12) and macrophage inflammatory protein-3alpha (MIP-3alpha, CCL20), and the SDF-1 receptor, CXCR4. To assist in phenotyping of SDF-1 + cells, specimens were also stained for CD20 (B cells). Positive staining for SDF-1 was identified in all PCNSL cases and in tonsil. In biopsy specimens, SDF-1 expression was localized to resident brain cells and, in 80% of specimens, CD20+ malignant lymphocytes. Tumor cells also stained positively for CXCR4. In contrast, although expression ofMIP-3alpha was detected in tonsil, no expression of this chemokine could be demonstrated in PCNSL biopsy specimens. Our observations raise the possibility of targeting the SDF-1-CXCR4 signaling pathway as a potential treatment for PCNSL.
Smith
Justine R
JR
Casey Eye Institute, Science University, Portland, OR 97239, USA.
Falkenhagen
Katherine M
KM
Coupland
Sarah E
SE
Chipps
Timothy J
TJ
Rosenbaum
James T
JT
Braziel
Rita M
RM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D054418:Chemokine CCL20; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000096:biosynthesis
C108355:CCL20 protein, human; C515255:CXCL12 protein, human; D054418:Chemokine CCL20; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins; D019718:Receptors, CXCR4