elastin and Carcinoma

Topics: Animals; Basement Membrane; Breast Neoplasms; Carcinoma; Cell Communication; Collagen; Elastin; Extracellular Space; Humans; Microbial Collagenase; Neoplasm Invasiveness; Neoplasm Metastasis; Receptors, Immunologic; Receptors, Laminin

The fluorescence of paired human breast malignant and normal tissue samples was investigated using a novel fluorescence spectroscopic (S3-LED) ratiometer unit with no moving parts. This device can measure the emission spectra of key native organic biomolecules such as tryptophan, tyrosine, collagen and elastin within tissues by using LED (light emitting diode) excitation sources coupled to an optical fiber. With this device, the spectral profiles of 11 paired breast cancerous and normal samples from 11 patients with breast carcinoma were obtained. In each of the 11 cases, marked increases in the tryptophan levels were found in the breast carcinoma samples when compared to the normal breast tissues. In the breast cancer samples, there were also consistently higher ratios of the 340 to 440 nm and the 340 to 460 nm intensity peaks after 280 nm excitation, likely representing an increased tryptophan to NADH ratio in the breast cancer samples. This difference was seen in the spectral profiles of the breast cancer patients regardless of whether they were HER2 positive or negative or hormone receptor positive or negative, and was found regardless of menopausal status, histology, stage, or tumor grade.

Topics: Adult; Aged; Area Under Curve; Breast; Breast Neoplasms; Carcinoma; Collagen; Discriminant Analysis; Elastin; Female; Humans; Middle Aged; Optical Imaging; ROC Curve; Spectrometry, Fluorescence; Tryptophan; Tyrosine

The intracellular domains of the membrane-anchoring regions of some precursors of epidermal growth factor (EGF) family members have intrinsic biologic activities. We have determined the role of the human proEGF cytoplasmic domain (proEGFcyt) as part of the proEGF transmembrane-anchored region (proEGFctF) in the regulation of motility and elastinolytic invasion in human thyroid cancer cells. We found proEGFctF to act as a negative regulator of motility and elastin matrix penetration and the presence of proEGFcyt or proEGF22.23 resulted in a similar reduction in motility and elastinolytic migration. This activity was counteracted by EGF-induced activation of EGF receptor signaling. Decreased elastinolytic migratory activity in the presence of proEGFctF and proEGFcyt/proEGF22.23 coincided with decreased secretion of elastinolytic procathepsin L. The presence of proEGFctF and proEGFcyt/proEGF22.23 coincided with the specific transcriptional up-regulation of t-SNARE member SNAP25. Treatment with siRNA-SNAP25 resulted in motility and elastin migration being restored to normal levels. Epidermal growth factor treatment down-regulated SNAP25 protein by activating EGF receptor-mediated proteasomal degradation of SNAP25. These data provide first evidence for an important function of the cytoplasmic domain of the human proEGF transmembrane region as a novel suppressor of motility and cathepsin L-mediated elastinolytic invasion in human thyroid carcinoma cells and suggest important clinical implications for EGF-expressing tumors.

Topics: Animals; Carcinoma; Cathepsin L; Cathepsins; Cell Movement; Cysteine Endopeptidases; Cytoplasm; Down-Regulation; Elastin; Epidermal Growth Factor; Female; Humans; Hydrolysis; Male; Models, Biological; Neoplasm Invasiveness; Protein Precursors; Protein Structure, Tertiary; Thyroid Neoplasms; Transfection; Tumor Cells, Cultured

The role of members of the insulin-like superfamily in human thyroid carcinoma is primarily unknown. Here we demonstrate the presence of RLN2 relaxin and relaxin receptor LGR7 in human papillary, follicular, and undifferentiated anaplastic thyroid carcinoma suggesting a specific involvement of relaxin-LGR7 signaling in thyroid carcinoma. Stable transfectants of the LGR7-positive human follicular thyroid carcinoma cell lines FTC-133 and FTC-238 that secrete bioactive proRLN2 revealed this hormone to act as a multifunctional endocrine factor in thyroid carcinoma cells. Although RLN2 did not act as a mitogen, it acted as an autocrine/paracrine factor and significantly increased anchorage-independent growth and thyroid carcinoma cell motility and invasiveness through elastin matrices. Suppression of LGR7 expression by LGR7-siRNA abolished the RLN2-mediated accelerated tumor cell motility. The increased elastinolytic activity correlated with enhanced production and secretion of the lysosomal proteinases cathepsin-D (cath-D) and cath-L forms hereby identified as new RLN2 target molecules in human neoplastic thyrocytes. We found the intracellular distribution of procath-L specifically altered in RLN2 transfectants, providing first evidence for selective actions of relaxin on the powerful elastinolytic cath-L production, storage, and secretion in thyroid carcinoma cells. Thus, relaxin enhances the oncogenic potential and acts as novel endocrine modulator of invasiveness in human thyroid carcinoma cells.

Topics: Adolescent; Adult; Aged; Carcinoma; Cathepsins; Cell Line, Tumor; Cell Movement; Child; Elastin; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Membrane Proteins; Middle Aged; Neoplasm Invasiveness; Protein Transport; Receptors, G-Protein-Coupled; Receptors, Peptide; Relaxin; RNA, Messenger; Signal Transduction; Thyroid Neoplasms; Transfection; Tumor Cells, Cultured

Elastosis in benign and malignant breast lesions was studied by light microscopic immunohistochemistry for elastin and by electron microscopy. Upon immunohistochemical examination for elastin, elastosis, particularly in scirrhous-type ductal carcinoma, showed two characteristic staining patterns: fibrously and intensely stained elastic fibers and evenly stained elastic masses. Elastic fibers showing increased fibrous staining occurred mainly in the stromal areas, and were considered to be newly formed because they consisted of tannic acid-positive amorphous components and abundant microfibrils. Evenly stained elastic masses were observed mainly in the periductal areas and showed less intense stainability. These masses consisted of numerous fine amorphous components with plentiful microfibrils. In some regions within these masses, there were condensed accumulations of irregularly arranged small amorphous components associated with only a few microfibrils. These amorphous components had an ill-defined outline and were occasionally associated with spiralling collagen fibrils and cell debris. On the basis of these findings, the periductal evenly stained elastic masses were thought to be formed by excessive production of elastic fibers and degradation of pre-existing and newly formed elastic fibers.

Topics: Breast Neoplasms; Carcinoma; Connective Tissue Diseases; Elastic Tissue; Elastin; Humans; Immunohistochemistry; Microscopy, Electron; Reference Values; Skin Diseases

An ultrastructural study on elastosis of human breast tumors was made with special attention to the periductal elastosis and the cell responsible for elastic fiber formation. The elastosis was found prominently in scirrhous type of duct carcinoma. In the area of mild periductal elastosis, the elastic fibers with many microfibrils and a tiny central elastin were seen around the periductal fibroblasts which were characterized by attenuated cytoplasms with aggregates of microfilaments and slightly developed rough endoplasmic reticulum. With the thickening of the periductal wall, such an area was replaced by abundant mature elastic fibers with peripheral microfibrils and a few intervening ordinary fibroblasts. Therefore, it was suggested that the periductal fibroblasts which transformed into ordinary fibroblasts during the development of elastosis were primarily concerned with the elastic fiber formation. In the interlobular tissue in which both fibroblasts and myofibroblasts were present, the elastic fibers were larger than those of the periductal area and had less microfibrils in their periphery. The relationship between microfibrils and elastin during the early elastosis, maturation process of the elastic fibers, and cell modulation of the fibroblasts in the breast elastosis were discussed.

Topics: Adenofibroma; Adult; Breast; Breast Diseases; Breast Neoplasms; Carcinoma; Elastic Tissue; Elastin; Female; Fibroblasts; Histocytochemistry; Humans; Middle Aged

Polymeric elastin was isolated and chemically characterized from 34 human breast cancers. There exists a good correlation between the histological and biochemical determinations of elastin; the breast cancer elastin resembles the other elastins isolated from ligamentum nuchae or aorta. Meanwhile it differs by its lower proline content and by its degree of crosslinking as determined by the ratio (Des + IDes/4)Lys. An elastinolytic activity (elastase) was found in human breast cancer extracts. This activity increased with the elastin content of the tumors.

Topics: Amino Acids; Breast Neoplasms; Carcinoma; Chemical Phenomena; Chemistry; Elastin; Female; Histocytochemistry; Humans; In Vitro Techniques; Pancreatic Elastase

Topics: Age Factors; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Elastic Tissue; Elastin; Microscopy, Electron; Pancreatic Elastase; Staining and Labeling