thymosin and Hyperplasia

The Dunning rat prostatic carcinoma is a model system where cell motility closely correlates with the metastatic phenotype. We have identified a novel gene, upregulated in the highly motile and metastatic Dunning cancer cell lines, that represents a new member of the thymosin-beta family, thymosin beta 15. Transfection of antisense thymosin beta 15 constructs into rat prostatic carcinoma cells demonstrates that this molecule positively regulates cell motility, a critical component of the metastatic pathway. Thymosin beta 15 levels are elevated in human prostate cancer and correlate positively with the Gleason tumor grade. Thymosin beta 15 may represent a potential new biochemical marker for human prostate cancer progression.

Topics: Actins; Amino Acid Sequence; Animals; Base Sequence; Biomarkers, Tumor; Carcinoma; Cell Movement; Cloning, Molecular; Gene Expression Regulation, Neoplastic; Humans; Hyperplasia; Male; Molecular Sequence Data; Neoplasm Metastasis; Organ Specificity; Prostate; Prostatic Neoplasms; Rats; Recombinant Fusion Proteins; RNA, Antisense; RNA, Messenger; RNA, Neoplasm; Thymosin; Tumor Cells, Cultured

This report describes the development of hyperplasia of both the thymus and the peripheral T-cell system with advancing age in the Buffalo rat. Buffalo/Mna rats do not show age-related thymic involution, but rather develop thymic hyperplasia with advancing age. This thymic growth is expansile and there is no infiltration of the surrounding tissues. Because the enlarging thymus occupies the thoracic cavity, most of the rats die of respiratory failure by the age of 24 months. Thymic enlargement is due to primary hyperplasia of cortical epithelial cells and the large number of proliferating lymphocytes. The hyperplastic epithelial cells are bizarre in shape and strongly positive when stained with Th-3 monoclonal antibody (MoAb), anti-thymosin antibody and anti-EGF antibody, but negative with Th-4 MoAb. The patterns of distribution of CD-5+, CD-4+ and CD-8+ lymphocytes within the hyperplastic thymus are similar to those seen in young rats of other species. The high level of T-cell emigration from the thymus to the periphery appears to persist throughout life, since the percentage of normal splenic T-cells also increase with advancing age and exceed 70% of the total by 24 months of age. This thymic enlargement with abnormal hyperplasia of cortical epithelial cells can be prevented by hypophysectomy.

Topics: Aging; Animals; Antibodies, Monoclonal; Epidermal Growth Factor; Epithelium; Female; Hyperplasia; Immunologic Techniques; Leukocyte Count; Male; Organ Size; Rats; Rats, Inbred BUF; Rats, Inbred Strains; Spleen; T-Lymphocytes; Thymosin; Thymus Gland

There was no statistically significant difference in the intensity of the cell-mediated immune response of tonsillar T cells among different pathological conditions of the tonsils nor among different age groups. The tonsillar cell population of the adult was smaller than that of the child. Tonsillar cells were separated into 3 fractions with different specific gravities. In tonsillar cells from adults, fraction III consisting mainly of small lymphocytes with a high specific gravity occupied a larger portion than in those from children. Fraction I consisting of cells with a low specific gravity had a greater number of cells in the swollen tonsils of children than in the tonsils of adults. However, the absolute numbers of the cells in fraction III in adults and in children were nearly the same. The proportion of T cells in fraction III was higher than in fraction I. Hence, the proportion of T cells in adults' tonsils is higher than in children's tonsils. The cells composing fraction I include some cells that have undergone blastoid transformation in response to various stimuli and some lymphoid cells that are ontogenetically immature T cells, besides mature T cells. The cells composing fraction III include fully mature T cells and the total cell population of fraction III does not differ significantly with age. It seems likely that the child's tonsil contains a larger number of cells under antigenic stimulation or in preparation for immune response than does the adult's tonsil.

Topics: Adult; Aging; Bacterial Proteins; Child; Concanavalin A; Humans; Hyperplasia; Immunity, Cellular; Lymphocyte Culture Test, Mixed; Middle Aged; Palatine Tonsil; T-Lymphocytes; Thymosin; Tonsillitis