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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of five autonomous sublines established independently from the transplantable hormone-dependent mouse mammary tumor, TPDMT-4, three but not two acquired metastatic potential. In in vitro culture using collagen gels, actinonin, an antibiotic protease inhibitor exerted a stronger growth-inhibiting effect on the metastatic than on the parent and non-metastatic tumors. Zymographic analysis demonstrated the active forms of gelatinases in the metastatic but not in the non-metastatic sublines and the complete inhibition of the enzyme activities by actinonin. Gelatinases/type IV collagenases might play an important role in tumor progression towards metastatic phenotype and actinonin may suppress tumor growth through inhibiting collagenase.
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PMID:Effects of an antibiotic protease inhibitor, actinonin on the growth within collagen gels of non-metastatic and metastatic mouse mammary tumors of the same origin. 763 45

Hypercalcemia is the most common paraneoplastic syndrome associated with cancer. This paper addresses the etiology and pathogenesis of hypercalcemia of malignancy and discusses the relative contributions of local and humoral effects on bone and renal calcium homeostasis. The roles of parathyroid hormone-related protein and other osteolytic cytokines are outlined. New biochemical markers that enable more specific monitoring of the response of bone metastases to treatment are introduced, including urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline. The clinical management and prevention of hypercalcemia is systemically outlined, including indications for bisphosphonate, glucocorticoid, and calcitonin therapy. The results of recent trials of bisphosphonate therapy for the prevention of tumor progression and its subsequent problems such as bone pain, fracture, and hypercalcemia also are discussed.
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PMID:Hypercalcemia and bone resorption in malignancy. 763 18

Thirty cases of hepatocellular carcinoma (HCC) were investigated immunocytochemically for expression of beta 1 integrin molecule and of collagen IV. Immunoreactivity was related to the tumour proliferation index, as detected by PCNA immunostaining, and to tumour size and grade. Membrane beta 1 integrin immunoreactivity was detected in the neoplastic cells of all cases, though two different staining patterns were clearly recognized. In 14 cases, beta 1 integrin immunoreactivity was confined to the cell-stroma interface, showing the same polarized pattern as the non-neoplastic cell counterpart. This staining pattern was associated significantly (P < 0.0001) with low PCNA labelling (i.e. less than 20 per cent of neoplastic cells showing nuclear immunostaining. Conversely, 16 cases showed non-polarized pericellular beta 1 integrin immunostaining. This staining pattern was significantly associated (P < 0.0001) with high PCNA labelling (more than 20 per cent of immunoreactive cells) and with tumour size greater than 4 cm in diameter (P < 0.0001). beta 1 Integrin, collagen IV, and PCNA immunoreactivities, however, did not correlate with the histological grade. The data emphasize that neoplastic progression of HCCs may be correlated with an aberrant expression of adhesion molecules and with a disruption of the collagen IV complement of basal membranes.
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PMID:Patterns of integrin common chain beta 1 and collagen IV immunoreactivity in hepatocellular carcinoma. Correlations with tumour growth rate, grade and size. 822 50

The effect of lysophosphatidic acid (LPA) on the proliferation of normal and tumor mouse mammary epithelial cells in primary, serum-free, collagen gel cell culture was evaluated. LPA stimulated the growth of normal mammary epithelial cells from mature virgin mice. The growth of pregnancy-dependent tumors (PDT) was generally stimulated, although the response was attenuated in some of these tumors compared to normal cells. In contrast, the growth of 70% of ovarian-independent tumors (OIT) was inhibited by LPA; the remainder were unaffected. LPA stimulated cAMP accumulation and phosphoinositide (PI) hydrolysis in normal, PDT, and OIT. Thus, the regulation of adenylyl cyclase and PI-specific phospholipase C by LPA is similar in normal and tumor cells. Pertussis toxin (PT) partially inhibited LPA-stimulated growth in normal cells but did not affect LPA-stimulated PI hydrolysis or cAMP accumulation. Thus, PT-sensitive and -insensitive proliferative pathways are activated. PT also inhibited LPA-stimulated growth of PDT but generally had no effect on the growth of OIT. These results show that the mitogenic response to LPA is attenuated in the hormone-dependent phenotype and switches to growth inhibition in hormone-independent tumors. Furthermore, LPA stimulates multiple signal transduction pathways mediated by PT-sensitive and -insensitive G proteins. The PT-sensitive pathways are not tightly coupled to the proliferative response to LPA in tumor cells. These data suggest that alterations in G protein function may occur during tumor progression.
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PMID:Analysis of the proliferative response to lysophosphatidic acid in primary cultures of mammary epithelium: differences between normal and tumor cells. 781 18

Overexpression of the ERBB2 receptor in transfectants of a human mammary epithelial cell line (MTSV1-7) is associated with a reduced ability to undergo morphogenesis in vitro and with a decreased level of expression of the E-cadherin and alpha 2 integrin genes. The inhibition of expression of the adhesion molecules has been shown to be at the level of transcription by using nuclear run-on assays and by following transcription of a reporter gene fused to 5' sequences of the E-cadherin gene. To relate the effects on gene transcription to a functional ERBB2 protein, signaling from the receptor was inhibited by the antibody 4D5, which blocks phosphorylation of ERBB2 on tyrosine residues and association of the protein with the GRB2/Sem5 protein. After treatment with the antibody 4D5, the ERBB2 transfectants regain the ability to form three-dimensional structures in collagen gels and the rates of transcription of the genes encoding the E-cadherin and the alpha 2 integrin subunit are restored to the levels seen in MTSV1-7neo cells. These results demonstrate that the inhibition of morphogenesis and transcription of specific adhesion molecules in human mammary epithelial cells can be affected by signals generated by the ERBB2 receptor and suggest a role for ERBB2 overexpression in tumor progression and metastasis.
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PMID:Overexpression of ERBB2 in human mammary epithelial cells signals inhibition of transcription of the E-cadherin gene. 791 48

The epithelial basal lamina composition and integrin expression profile of normal and neoplastic human prostate was characterized using immunohistochemical analysis of frozen samples. The major components of the basal lamina surrounding normal acini were laminin, type IV collagen, entactin, and type VII collagen with variable amounts of tenascin. The basal lamina of neoplastic acini had a similar composition, except for the loss of type VII collagen, which was observed in all grades of carcinoma. The basal cells of the normal prostate express the alpha 6-, beta 1-, and beta 4-integrin subunits, suggesting that both the alpha 6 beta 1- and alpha 6 beta 4-integrin complexes are formed. In prostate carcinoma there is a complete loss of beta 4 expression and the alpha 6- and beta 1-integrin subunits, which are restricted to the basal and basal lateral surfaces of basal cells, are distributed diffusely throughout the cytoplasmic membrane. The differential expression of type VII collagen and beta 4 are discussed in relationship to their possible role in tumor progression.
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PMID:Differential expression of extracellular matrix molecules and the alpha 6-integrins in the normal and neoplastic prostate. 803 Jul 47

Exogenous HGF/SF converts subconfluent cultures of NBT-II epithelial carcinoma cells into mobile fibroblast-like cells while being only mitogenic for cells maintained at high density. To investigate the potential role of such factor in tumor progression, we generated HGF/SF-producing NBT-II cells by transfection with an expression plasmid containing human HGF/SF cDNA. HGF/SF-producing cells also exhibit a fibroblastic phenotype. Media conditioned by these cells are potent inducers of in vitro tubulogenesis which can be inhibited with specific anti-HGF/SF antibodies; these antibodies are also able to reverse the scattered phenotype of the HGF/SF-producing cells. In addition spheroids of HGF/SF-producing cells are dispersed into 3D collagen gels suggesting an increase of invasive properties of these cells. When injected in nude mice, these HGF/SF-producing cells induce tumors appearing more rapidly than did those obtained with untransfected cells. These results show that HGF/SF can promote motility and invasive properties of NBT-II bladder carcinoma cells and also confers a tumorigenic advantage when acting as an autocrine factor.
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PMID:Creation of an hepatocyte growth factor/scatter factor autocrine loop in carcinoma cells induces invasive properties associated with increased tumorigenicity. 813 12

Type 1 transforming growth beta (TGF-beta 1) is a multifunctional regulator of cellular differentiation, motility and growth. It is capable of inhibiting or stimulating these processes depending on cell type, cell density, culture conditions and TGF-beta 1 concentration. TGF-beta 1 regulates growth, in part, by inducing the expression and secretion of various types of collagen, which participate in the control of cell adhesion and migration, as well as growth. TGF-beta 1 also regulates cell growth by controlling the response to epidermal growth factor (EGF) and other growth factors, in ways that can either decrease or increase their growth-promoting effects. Alterations in both negative and positive growth responses to TGF-beta 1 play important roles in tumor progression. Loss of sensitivity to growth inhibition by TGF-beta 1 can occur as a result of decreased expression of collagen. Acquisition of sensitivity to growth stimulation, and autocrine transformation by TGF-beta 1, are associated with aberrant EGF receptor regulation. Aberrant growth factor receptor regulation by TGF-beta 1 may be mediated by a protein kinase C (PKC)-dependent pathway which inhibits degradation of growth factor receptor/ligand complexes. The evidence reviewed is consistent with a minimal two-step mechanism for autocrine transformation, which involves production of growth factor and enhanced cellular response as a result of aberrant membrane traffic. Defects in membrane traffic regulation may provide an explanation for common alterations in tumor cell response to both multiple growth inhibitors and growth stimulators, and may also suggest novel approaches to cancer chemotherapy.
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PMID:Transforming growth factor beta and the cell surface in tumor progression. 828 11

The distribution of the basement membrane (BM) components, laminin, type IV collagen and type VII collagen were studied immunohistochemically in benign and malignant growths of the mammary epithelium of the dog and cat. Intact BMs were found in benign growths, but in well-differentiated malignant tumours they were generally discontinuous, and missing in poorly differentiated carcinomas. An increase in the histological grade of atypia was accompanied by a more marked disruption or fading of BM. Monoclonal antibody (LH 7.2) proved useful in demonstrating type VII collagen in tumours in which massive proliferation of blood vessels made the evaluation of BM features with antibodies to laminin and type IV collagen difficult. Type VII collagen is present in BM of the mammary epithelium but not under the endothelium of blood vessels; it may therefore enhance the value of BM markers as aids in the study of neoplastic progression.
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PMID:Basement membrane components in mammary tumours of the dog and cat. 830 Sep 12

The cell-surface heterodimers of the integrin family of molecules, which mediate cell-cell and cell-substratum interactions, are likely to be functionally relevant in local and metastatic tumor growth. In the present study we have analyzed whether the alpha 3/beta 1 receptor for collagen, laminin and fibronectin undergoes changes in expression during tumor progression in cutaneous malignant melanoma (CMM). The results of this study have demonstrated that, while low levels of VLA3 expression are detectable in benign lesions, in primary melanomas the heterodimer undergoes progressive increase in expression which correlates with the degree of dermal invasiveness. Metastatic lesions were found VLA3 positive in 82% of cases. Furthermore, the heterodimer is homogeneously expressed in multiple autologous metastases. The presence of VLA3 correlates with detection of at least one of the ligands in 45% of the cases studied. These findings provide additional evidence that tumor progression in CMM is associated with changes in integrin phenotypes which include the alpha 3/beta 1 heterodimer.
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PMID:Integrin expression in cutaneous malignant melanoma: association of the alpha 3/beta 1 heterodimer with tumor progression. 847 49


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