Melanoma-inhibiting activity (MIA/CD-RAP) is expressed in a variety of malignant tumors of mainly neuroectodermal origin.
BACKGROUND
The identification of tumor-specific antigens is an important topic for potential therapeutic and diagnostic applications. Melanoma-inhibiting activity (MIA/CD-RAP), a protein involved in the regulation of tumor growth, invasion, dissemination and immunoreactivity in melanomas and other tumors, is expressed by almost all melanomas and melanoma metastases screened to date so far. Elevated levels of melanoma-inhibiting activity (MIA/CD-RAP) have also been measured in a subgroup of patients with advanced stage breast carcinomas.


METHODS
To further evaluate the extent and distribution of MIA/CD-RAP expression, early passage melanoma, glioma and other tumor cell lines as well as non-malignant cell lines were screened for the expression of MIA/CD-RAP by PCR, Western blot and immunohistochemistry.


RESULTS
All melanomas tested (n = 19) expressed high levels of MIA mRNA and protein. A high incidence of MIA expression was also found in glial tumors (6 out of 27). In contrast, MIA message (mRNA) could not be detected in non-glial CNS-tumors (n = 13). In addition, in CSF of patients harboring a brain tumor, significant higher levels of MIA protein were detectable compared to the systemic values. MIA/CD-RAP-message was detectable in 7 out of 20 systemic tumors, mainly carcinomas of the colon (2 out of 2) and, in low levels, in 8 out of 20 normal non-transformed cell cultures, for example fibroblasts and peripheral lymphocytes. These data indicate that MIA/CD-RAP is widely expressed in human and murine primary cell cultures and cell lines, with nevertheless relative high specificity for melanocytic tumors. Measurements of MIA protein in the cerebrospinal fluid (CSF) and serum of patients harboring metastatic melanoma revealed higher levels in the CSF than in serum. To address functional aspects of MIA/CD-RAP expression, we stably transformed a MIA/CD-RAP-negative glial tumor cell line to express MIA/CD-RAP. When tested in colony forming assay (CFA), these clones showed a marked reduction in colony formation.


CONCLUSIONS
According to these results, MIA/CD-RAP seems to exert a general function for invasive and metastatic tumors.
Hau
Peter
P
Department of Neurology, University of Regensburg, Germany. peter.hau@bkr-regensburg.de
Apfel
Rainer
R
Wiese
Petra
P
Tschertner
Ines
I
Blesch
Armin
A
Bogdahn
Ulrich
U
D016543:Central Nervous System Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000556:secondary; D016326:Extracellular Matrix Proteins; D005910:Glioma / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000556:secondary; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger