concanavalin-a and Hypertrophy

Intradermal administration of concanavalin A, a potent T-cell mitogen, into an ear lap resulted in activation of chondrogenesis and stimulation of epidermis proliferation. This proliferation is sometimes invasive in character (pearls and epidermal nests form in the underlying connective tissue) but never turns into true cancerous lesions. This reaction can be delayed, but not prevented, by the prostaglandin inhibitor indomethacin. Stimulation of epidermis proliferation was also caused by administration of other immunomodulators, such as carrageenan type IV, Moloney sarcoma development, and rarely in the course of GvHr, but to much lesser degree than with concanavalin A. It is suggested that the same growth factors, which are mediators of local chondrocyte stimulation, are also mediators of keratinocyte activation.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Marrow Transplantation; Carrageenan; Chondrocytes; Concanavalin A; Drug Eruptions; Ear Diseases; Ear Neoplasms; Ear, External; Epidermis; Epithelium; Female; Graft vs Host Reaction; Hyperplasia; Hypertrophy; Indomethacin; Keratinocytes; Keratins; Male; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Inbred DBA; Mice, Inbred ICR; Mice, SCID; Moloney murine sarcoma virus; Precancerous Conditions; Sarcoma, Experimental; Transplantation, Heterotopic

Resting chondrocytes do not usually undergo differentiation to the hypertrophic stage and calcification. However, incubating these cells with concanavalin A resulted in 10-100-fold increases in alkaline phosphatase activity, binding of 1,25(OH)2-vitamin D3, type X collagen synthesis, 45Ca incorporation into insoluble material, and calcium content. On the other hand, other lectins tested (including wheat germ agglutinin, lentil lectin, pea lectin, phytohemagglutinin-L, and phytohemagglutinin-E) marginally affected alkaline phosphatase activity, although they activate lymphocytes. Methylmannoside reversed the effect of concanavalin A on alkaline phosphatase within 48 h. Concanavalin A did not increase alkaline phosphatase activity in articular chondrocyte cultures. In resting chondrocyte cultures, succinyl concanavalin A was as potent as concanavalin A in increasing alkaline phosphatase activity, the incorporation of [35S]sulfate, D-[3H]glucosamine, and [3H]serine into proteoglycans, and the incorporation of [3H]serine into protein, although concanavalin A, but not succinyl concanavalin A, induced a rapid change in the shape of the cells from flat to spherical. These findings suggest that concanavalin A induces a switch from the resting, to the growth-plate stage, and that this action of concanavalin A is not secondary to changes in the cytoskeleton. Chondrocytes exposed to concanavalin A may be useful as a novel model of endochondral bone formation.

Topics: Alkaline Phosphatase; Animals; Calcification, Physiologic; Cartilage; Cell Movement; Cell Size; Cells, Cultured; Collagen; Concanavalin A; DNA; DNA Replication; Enzyme Induction; Growth Substances; Hormones; Hypertrophy; Male; Mannosides; Methylmannosides; Proteoglycans; Rabbits; Receptors, Calcitriol; Uronic Acids

The hypertrophic duct epithelium of the pancreas, including the pyloric gland metaplasia, mucous cell hypertrophy and ductal papillary hyperplasia were studied clinico-pathologically and histochemically to examine their precancerous character. A total of 180 surgical and autopsy specimens (90 pancreata with cancer and 90 pancreata without cancer) were analysed. The overall incidence of these three types of hypertrophic epithelium in the pancreas cancer was much higher than that in the pancreas without cancer. These hypertrophic lesions appeared most frequently in the interlobular duct. The histochemical study revealed the presence of a new type of glycoprotein in these hypertrophic duct epithelia, however, this substance was not detected in the cancer cells nor in the normal epithelium. This suggests that these hypertrophic lesions may not be the precursors of cancer but rather the coexistent lesions of pancreas cancer.

Topics: Adult; Aged; Concanavalin A; Cytoplasm; Epithelium; Glycoproteins; Glycosaminoglycans; Histocytochemistry; Horseradish Peroxidase; Humans; Hypertrophy; Middle Aged; Mucoproteins; Pancreatic Diseases; Pancreatic Ducts; Pancreatic Neoplasms; Precancerous Conditions; Staining and Labeling