Open AccessTwo human melanoma cell‐line variants with enhanced in vivo tumor growth and metastatic capacity do not express the β 3 integrin subunit
Author(s) -
BOUKERCHE Habib,
BENCHAIBI Miloud,
BERTHIERVERGNES Odile,
LIZARD Gerard,
BAILLY Maryse,
BAILLY Mireille,
McGREGOR John L.
Publication year - 1994
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1994.tb18647.x
Subject(s) - melanoma , cell culture , in vivo , cancer research , metastasis , flow cytometry , alpha v beta 3 , biology , cell growth , integrin , cell , beta (programming language) , pathology , microbiology and biotechnology , medicine , cancer , genetics , computer science , vitronectin , programming language
The α v β 3 integrin complex is thought to play an important role in in vivo melanoma tumor growth and metastasis. However, not all human metastatic melanomas, present in lymph node biopsies, express α v β 3 . In this study, we have investigated the possibility that certain melanoma cell lines can grow aggressively in vivo in the absence of α v β 3 expression. Established human melanoma cell lines (M 3 Da., M 4 Beu.) were isolated from an achromic skin metastasis of lymph nodes. Two stable variants (7GP, T1P26), derived from a poorly metastatic M 4 Beu. melanoma cell line, were isolated by sequential selection for spontaneous metastasis formation in an immunosuppressed newborn rat model. Flow‐cytometry analysis shows an absence of the β 3 integrin subunit (less than 2% of parental levels) in the two variant melanoma cell lines (7GP, T1P26) compared to M 3 Da. and M 4 Beu. cell lines which express a relatively high number of β 3 subunits. The expression levels of the integrin subunits β 1 , β 5 , β 6 and α v were found to be similar for all four melanoma cell lines. Northern blot analysis confirmed the absence of β 3 in 7GP or T1P26 cell lines and its presence in M 3 Da. and M 4 Beu. Moreover, similar levels of α v transcript were present in the four melanoma cell lines. The functional effect of the absence of β 3 was investigated by subcutaneously implanting the variants and the melanoma cell lines in nude mice. Variant 7GP and T1P26 cell lines yielded tumors which were larger and grew at a faster rate than tumors in M 3 Da. or M 4 Beu. cell lines. The β 3 integrin subunit was not detectable on the surface of cells harvested from tumors after 20 or 35 days. Similarly, subcutaneous innoculation of the two variants into immunosuppressed newborn rats gave rise to extensive spontaneous lung metastases compared to the M 4 Beu. cell line. These results provide evidence that a population of melanoma cells can grow aggressively in vivo and metastasize in the absence of β 3 or α v β 3 integrin complex. Our results may have clinical relevance and suggest that certain types of melanomas in patients may grow and spread in the absence of the α v β 3 integrin complex.