[Molecular characteristics of leiomyoma uteri based on selected compounds of the extracellular matrix].
Leiomyoma is a monoclonal benign tumor. It is often located in the muscle layer of the uterus in women of reproductive age. Its growth is accelerated by pregnancy and hormonal therapy. Its growth also depends on the concentration of sex hormones. Growth factors and cytokines may also participate in the formation of leiomyomas. The modulation of mitotic activity and abnormal extracellular matrix production are key elements of tumor growth. Elements of the TGFbeta superfamily are crucial factors in the proliferation of neoplasmic cells. TGF-beta1 and -beta3 stimulate the synthesis of various components of the extracellular matrix, but they also down-regulate the synthesis of proteinases which degrade the matrix, often leading to excessive overdeposition of connective tissue. Collagen types 1 and 3 are the main structural components of the extracellular matrix. The biosynthesis of collagens requires, among others, the action of procollagen C-endopeptidase, a protein of the BMP-1/mTLD subfamily. BMP-1/mTLD-like proteinases remove the carboxyl propeptides of procollagens 1, 2, and 3. Removal of the C-propeptides decreases the solubility of procollagens about 1000-fold to a concentration critical for their spontaneous self-assembly to collagen fibrils. Different substrates of BMP-1/mTLD are prolysyl oxidase, gamma2 chain of prolaminin, procollagen type VII, miostatin, dentin matrix protein 1, and perlekan. Due to the activation of various substrates by BMP-1/mTLDs, they are important regulators of the production of the extracellular matrix and its quality as well as of antiangiogenic responses by producing a factor from the basal membrane compound called perlekan. The BMP-1/mTLDs influence the formation of dorsal ventral patterning in embryos by releasing BMP-2/4 from the inhibitory protein chordin. Another aspect is induction of the development of muscle and neural tissue by activation of GDF8 and GDF11 as well as the regulation of growth and cell proliferation by releasing TGF-beta1 and -beta3 from latent complexes. Another yet poorly understood aspect is the evolution of neoplastic cells based on other than molecular genetic mechanisms. The detectable karyotype anomalies in tumor cells constitute just 40%. Therefore in this review the possible roles of extracellular matrix compounds and regulatory factors in the pathology of leiomyoma are discussed.
Auguściak-Duma
Aleksandra
A
Katedra i Zakład Biologii Molekularnej i Genetyki, Slaski Uniwersytet Medyczny. alsieron@sum.edu.pl
Sieroń
Aleksander L
AL
D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007889:Leiomyoma / Q000503:physiopathology*; D008666:Metalloendopeptidases / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism; D014594:Uterine Neoplasms / Q000503:physiopathology*
D019485:Bone Morphogenetic Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C491555:PCOLCE protein, human; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D008666:Metalloendopeptidases; C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1