A factor found in the IgG fraction of serum of patients with paraneoplastic bilateral diffuse uveal melanocytic proliferation causes proliferation of cultured human melanocytes.
OBJECTIVE
To determine if there is a factor in the serum of patients with bilateral diffuse uveal melanocytic proliferation (BDUMP) that causes melanocytic proliferation.


METHODS
Human melanocytes and melanoma cells were grown and exposed to serum or plasma of patients with BDUMP, other neoplastic conditions, or control media. Preliminary studies using serum were conducted in an unmasked fashion. In addition, IgG-depleted and IgG-enriched plasma was also tested in a similar fashion. Experiments using plasma were conducted triple masked. To show that the proliferation was melanocyte selective, human dermal fibroblasts, keratinocytes, and ovarian cancer cells were treated with plasma of the BDUMP cases or controls, and the effect of this exposure on their proliferation was quantified.


RESULTS
At 72 hours, the serum of BDUMP patients caused statistically significant increased proliferation of normal human melanocytes. Further studies at 6 days demonstrated similar findings. In addition, melanocytes grown in BDUMP serum exhibited a disorganized morphology with foci of multilayered cells. Cultured melanoma cells also showed statistically significant increase in growth in serum from BDUMP patients compared with controls. Masked plasma studies further confirmed these findings and showed that the IgG fraction appeared to contain the melanocyte growth-stimulating factor. The human fibroblasts, keratinocytes, and ovarian cancer cells did not show an increase in growth with the BDUMP plasma treatment.


CONCLUSIONS
Patients with BDUMP have a factor in the IgG fraction that selectively causes melanocyte proliferation. How it causes proliferation of human melanocytes and melanoma cells needs to be further elucidated.
Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA.
Sarah L
SL
Miles
Richard M
RM
Niles
Sean
S
Pittock
Richard
R
Vile
John
J
Davies
Jeffrey L
JL
Winters
Nakhleh E
NE
Abu-Yaghi
Axel
A
Grothey
Mustaqeem
M
Siddiqui
Judith
J
Kaur
Lynn
L
Hartmann
Kimberly R
KR
Kalli
Larry
L
Pease
Daniel
D
Kravitz
Svetomir
S
Markovic
Jose S
JS
Pulido
D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007155:Immunologic Factors / Q000494:pharmacology*; D008544:Melanocytes / Q000473:pathology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology; D059545:Paraneoplastic Syndromes, Ocular / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000166:cytology; D014604:Uveal Neoplasms / Q000276:immunology* / Q000473:pathology
D007074:Immunoglobulin G; D007155:Immunologic Factors