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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Double-label immunofluorescence was used to monitor basement-membrane composition and integrity in 22 human colon polyps, 36 adenocarcinomas and 2 metastases. Cryostat sections were stained with polyclonal anti-laminin anti-serum combined with monoclonal antibodies (MAbs) to all major basement-membrane components (laminin, entactin/nidogen, collagen type IV and large heparan sulfate proteoglycan), as well as to keratin 8. In all adenocarcinomas, including mucinous, basement membranes were altered more at the invasive front than in the parenchyma. The degree of this alteration was inversely correlated with the level of tumor differentiation. An uncoordinated loss of basement membrane components (dissociation of markers), previously described by us in rat colon adenocarcinomas, was also found in human tumors. In the great majority of adenocarcinomas a pronounced stromal reaction was seen. It was manifested by the presence of fibrillar deposits of basement-membrane components, mainly of collagen type IV and/or heparan sulfate proteoglycan. This reaction was never observed in polyps and may be derived from myofibroblasts reported to accumulate in colon cancer stroma. The combined use of antibodies to basement-membrane components and to a specific keratin may constitute an adequate immunohistochemical test for the presence of invasion, and may be useful in the histologic analysis of polyps, especially in dubious cases.
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PMID:Distribution of individual components of basement membrane in human colon polyps and adenocarcinomas as revealed by monoclonal antibodies. 137

The development of the basal lamina (BL), the key structure of the basement membrane (BM), was investigated in three xenografted human carcinomas of the sigmoid colon (CA 1), the lung (L 261), and the hypopharynx (H-Stg 1) following heterotransplantation to athymic mice. The study involved the use of electron microscopy and indirect immunofluorescence techniques employing highly specific antibodies against the intrinsic BL components, heparan sulfate proteoglycan, laminin and type-IV collagen. Following transplantation, the extracellular matrix material of the transplanted tumors decomposed and was phagocytozed by invading macrophages within 1 to 2 days. During this stage, no specific binding of the applied antibodies to BL components could be detected within the xenografts. Following the ingrowth of host-derived connective tissue between days 2 to 6, small fluorescence-positive granules appeared within the cytoplasm and around those tumor cells that were located close to the invaded strands of connective tissue. Ultrastructurally, typical secretory granules were detectable in the cytoplasm of many xenografted carcinoma cells. Thereafter, a tannic acid-positive, patchy material appeared in the extracellular space of CA 1 and L 261 and aggregated to form small fragments of a discontinuous BL. In the H-Stg 1 xenografts, this material assembled to form continuous mono-, bi- and multi-layered structures. Large amounts of excess BL material remained accumulated in the L 261 and H-Stg 1 xenografts until the end of the observation period (day 24). These findings reveal that discontinuities of the BL occur independent of the active invasion processes of tumor cells, since xenografted human carcinomas neither grow invasively nor metastasize in nude mice. Moreover, they confirm that these discontinuities are not caused by a quantitatively insufficient production of BL material, but rather arise from qualitative imbalances of the composition of the synthesized BL material.
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PMID:Development of the basal lamina in xenografted human carcinomas: an ultrastructural and immunohistochemical study. 181 85

Fibronectin plays a major role in the adhesion of many cell types. The extent of cell adhesion in vitro is related not only to the ability of the cells to interact with matrix-bound fibronectin, when it is present, but also to the synthesis or lack of synthesis of fibronectin by the cells, and to the lack of deposition of synthesized fibronectin into an insoluble matrix surrounding the cells. Many malignant cells, regardless of whether they synthesize subnormal or normal amounts of fibronectin, fail to deposit that fibronectin into a surrounding insoluble matrix. The lack of fibronectin around such cells appears to reflect a general absence of extracellular matrix since other matrix components, such as collagen, laminin, and heparan sulfate proteoglycan, are concomitantly missing. Cells that lack their own cell surface fibronectin due either to lack of deposition or to lack of synthesis can nevertheless adhere to insoluble fibronectin matrices elaborated by other cells. These cellular characteristics appear to be associated with cell migration in vivo during embryogenesis, and the same characteristics may enhance the invasive potential of malignant cells. The remarkable effects that fibronectin has on cellular adhesion and the association of lack of extracellular matrix components with poorly differentiated and highly metastatic tumors in vivo mandates that more be learned about the molecular and cellular details of the interactions of cells with their surrounding matrix. Important information concerning tumor invasion will parallel such an understanding and may eventually become the basis for therapeutic approaches.
Cancer Metastasis Rev 1984
PMID:Fibronectin in cell adhesion and invasion. 632 88

Tumors were developed from the mouse teratocarcinoma-derived endodermal cell line PF HR-9 by subcutaneous injections in syngeneic mice of large numbers of cells previously cultured for several years at high cell density. Cell cultures were established from the tumors and the cells were cloned. The cloned sublines were highly malignant in vivo and tumor metastases were occasionally observed. The tumors contained abundant extracellular material, which was distinctly laminated and contained type IV collagen, laminin, and heparan sulfate proteoglycan. The tumorigenic sublines were also shown to have retained markers of the original cells, such as the cytoskeletal proteins Endo A and B. These cell lines should be useful for biosynthetic studies on basement membrane and cytoskeletal components and the tumors for isolation of these macromolecules and their mRNAs.
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PMID:Clonal tumorigenic endodermal cell lines producing basement membrane components. 669 49

Bone resorption resulting from the metastatic human melanoma cell line (A375) was investigated morphologically using an experimental model of bone metastases in nude mice. An injection of A375 (1 x 10(5)) in the left ventricle produced multiple osteolytic lesions. Many TRAPase-positive multinucleated cells, identified by EM as osteoclasts, were observed on the bone surface at the site of metastases. The findings suggest that bone resorption was caused by osteoclasts developed in the presence of tumor cells. Even where tumor cells were juxtaposed to bone surface, small and flat TRAPase-positive cells were shown to exist on the bone surface. Thus, bone resorption was mainly associated with the occurrence of osteoclasts. A large number of osteoclast progenitor cells were also observed adjacent to tumor cells and/or stromal cells located apart from bone, indicating possible participation of tumor cells and/or stromal cells in the differentiation of osteoclasts. Ultrastructurally, stromal cells and/or extracellular matrices were present between tumor cells and osteoclast progenitor cells. Immunohistochemical observation clarified the localization of heparan sulfate proteoglycan (HSPG) and fibronectin (FN) around osteoclast progenitor cells. These findings suggest that they play an important role in providing a microenvironment favorable for osteoclast differentiation and activation. The immunohistochemical localization of IL-6, PGE2, and TGF-alpha also indicates that they are involved in osteoclast differentiation and activation. In conclusion, bone resorption at the metastatic sites of A375 is mediated via osteoclasts and A375 cells may be involved in the differentiation and activation of osteoclasts in association with stromal cells, extracellular matrices (HSPG, FN) and osteotropic cytokines (IL-6, PGE2, TGF-alpha).
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PMID:Bone resorption induced by a metastatic human melanoma cell line. 778 38

Serial cryostat sections of 160 human breast lesions and of 9 lymph-node metastases were studied by indirect immunofluorescence. We used monoclonal antibodies (MAbs) to lining-epithelium-specific keratin 8 and to myoepithelium-specific keratin 17 in combination with polyclonal and monoclonal antibodies to major basement membrane components, laminin, collagen type IV, entactin/nidogen, and large heparan sulfate proteoglycan (perlecan) core protein. Continuous basement membranes adjacent to a basal layer of keratin-17-positive myoepithelial cells were typical for normal, benign and in situ carcinomatous structures. In invasive and metastatic structures, always formed by keratin-8-positive tumor cells, basement membranes were found only rarely and with conspicuous fragmentations. This lack of basement membranes correlated with loss of myoepithelium identified by staining for keratin 17. In comedo structures of invasive ductal carcinomas and in papillary carcinomas, fibrovascular complexes with numerous blood vessels and deposition of basement membrane material were often seen in the stroma. Immunomorphological analysis of 41 cases of doubtful diagnosis at intra-operative biopsy was also performed. A combination of MAbs to keratins 8 and 17, and to basement membrane components, made it possible to distinguish between morphologically similar benign and malignant proliferations and to detect single-cell invasion of the stroma. This combination of antibodies may be recommended as an auxiliary immunomorphological tool for differential diagnosis of intra-operative breast biopsies in dubious cases.
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PMID:Myoepithelial and basement membrane antigens in benign and malignant human breast tumors. 842 64

Heparan sulfate (HS) functions as a co-factor in several signal-transduction systems that affect cellular growth, differentiation, adhesion and motility. HS, therefore, may also play a role in the malignant transformation of cells, tumor growth, cell invasiveness and the formation of tumor metastases. To explore this hypothesis, we analyzed the expression of HS and heparan sulfate proteoglycan (HSPG) in histological sections of human lung-cancer tissues and assayed for the presence of HSPGs in extracts of human lung-cancer cell lines, using a panel of native HS-, delta-HS- and HSPG (syndecan, glypican, CD44 and perlecan) core protein-specific monoclonal antibodies. Compared to normal epithelia, non-small-cell lung carcinomas, particularly poorly differentiated tumors, often expressed reduced amounts of the major cell surface-associated HSPGs (most consistently of syndecan-1). CD44 or CD44-variant proteins, in contrast, were found on all tumor cells, irrespective of their differentiation. Perlecan, a matrix-associated HSPG found in the basement membrane of normal bronchial epithelium, was consistently undetectable in invasive bronchogenic carcinomas. Staining reactions for native HS were consistently reduced in squamous-cell lung carcinomas, in the cells in contact with the stroma and in the less differentiated areas of these tumors. Reactions for delta-HS, however, were not reduced, suggesting a structural change in the HS of these tumor cells. Poorly differentiated adenocarcinomas, in contrast, yielded strong HS and delta-HS reactions. Marked differences in HSPG expression also were observed among various non-small-cell lung carcinoma cell lines. Our results suggest that poorly differentiated lung tumors have markedly altered patterns of HSPG expression, which may contribute to their invasive phenotype.
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PMID:Heparan sulfate proteoglycan expression in human lung-cancer cells. 922 15

In situ carcinomas must penetrate their own basement membrane to be classified as invasive, and subsequently infiltrate surrounding connective tissue and cross vascular basement membranes to metastasize hematogenously. Accordingly, in many studies, integral basement membrane components, including type IV collagen, laminin, and heparan sulfate proteoglycan, have been localized in a spectrum of tumors to gain insight into their role in neoplasia. A number of recently identified extracellular matrix molecules and isoforms of the aforementioned proteins have been localized to the basement membrane zone, illustrating another level of biochemical heterogeneity in these structures. As the complexity of these matrices becomes more apparent, their roles in maintaining homeostasis and in tumor biology falls into question. Of the new group of collagens localized to the basement membrane zone, type XV was the first to be characterized (Cell Tissue Res, 286:493-505, 1996). This nonfibrillar collagen has a nearly ubiquitous distribution in normal human tissues via a strong association with basement membrane zones, suggesting that it functions to adhere basement membrane to the underlying stroma. To begin investigation of this protein in malignant tumors, we have localized type XV in human colonic adenocarcinomas and compared its distribution with that of type IV collagen and laminin. Collagens XV and IV and laminin were found in all normal and colonic epithelial, muscle, fat, neural, and vascular basement membrane zones, as shown previously. In moderately differentiated, invasive adenocarcinomas, laminin and type IV collagen were sometimes observed as continuous, linear deposits around some of the malignant glands, but more often they were seen in either discontinuous deposits or were completely absent. In contrast, type XV collagen was characterized as virtually absent from the basement membrane zones of malignant glandular elements in moderately differentiated tumors. Nevertheless there were also similarities; all 3 proteins were usually present in the stroma and adjacent vascular basement membrane zones surrounding invasive glands. The loss of type XV collagen from these malignant epithelial basement membrane zones and its increased interstitial expression suggests a role for this protein in the invasive process and the possibility that it may provide a sensitive indicator of tumor invasion.
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PMID:Type XV collagen in human colonic adenocarcinomas has a different distribution than other basement membrane zone proteins. 1074 80

Syndecan-1 (CD138), a cell-surface heparan sulfate proteoglycan, is involved in cell-cell, cell-matrix interaction and growth factor binding. Loss of expression of syndecan-1 in tumor cells leads to decreased intercellular cohesion, increased potential for tumor invasiveness, and metastatic spread. Furthermore, induction of syndecan-1 expression in the tumor stroma has been postulated to promote tumor angiogenesis via its binding to growth factors such as basic fibroblast growth factor. Although syndecan-1 expression within tumor cells has been investigated in head and neck squamous cell carcinoma, stromal expression has not been studied in detail. We analyzed 38 cases of head and neck squamous cell carcinoma by immunohistochemical staining for syndecan-1 expression within the stroma. The expression of syndecan-1 within tumor cells of various histologic grades of differentiation, squamous cell carcinoma in situ cells, and benign squamous epithelium was also determined. Variable levels of diminished syndecan-1 expression were noted within the dysplastic cells of 9 of 16 (60%) squamous cell carcinoma in situ lesions and in all 38 (100%) invasive squamous cell carcinoma. In general, higher levels of syndecan-1 expression were observed in the well-differentiated tumors, in contrast to significant reduction of expression seen in poorly differentiated tumors. Syndecan-1 expression was observed within the stroma (in fibroblasts) surrounding infiltrating carcinoma cells in 28 of 38 (74%) cases. The intensity of syndecan-1 staining within the stroma showed generally an inverse correlation with the degree of tumor cell differentiation. Syndecan-1 expression was not detected in the stroma beneath normal squamous epithelium or adjacent to areas of squamous cell carcinoma in situ. We conclude that induced expression of syndecan-1 in the stroma surrounding tumor cells of invasive head and neck squamous cell carcinoma is a frequent event. The increased stromal syndecan-1 expression, coupled with its loss from the surface of carcinoma cells, may contribute to tumor cell invasion and the development of metastases.
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PMID:Induced expression of syndecan-1 in the stroma of head and neck squamous cell carcinoma. 1292 Feb 24

Syndecan-1, a cell-surface transmembrane heparan sulfate proteoglycan, has been reported to correlate with the biologic behavior of malignant tumors in various organs. We examined the correlation between the expression of syndecan-1 at the protein and mRNA levels and clinicopathologic features of 37 intrahepatic cholangiocarcinomas (ICCs). Noncancerous bile duct epithelial cells showed basolateral membranous expression of syndecan-1, whereas ICC cells showed membranous and also diffuse cytoplasmic expression. In situ hybridization demonstrated a distribution of syndecan-1 mRNA similar to that of the protein in carcinoma tissue, suggesting that syndecan-1 expression in ICC is regulated at the transcriptional level. Reduction of syndecan-1 expression in carcinoma was associated with poor histological differentiation (P <0.01): syndecan-1 expression was intense and extensive in well-differentiated (10 cases) and largely negative or weakly positive in poorly differentiated (13 cases) adenocarcinoma, and its expression in moderately differentiated tumors (14 cases) was intermediate. Patients with ICCs demonstrating negative or weak expression of syndecan-1 frequently had lymph node metastases and had a rather poor prognosis after surgical resection compared with those whose tumors demonstrated moderate or strong expression (P <0.05). However, syndecan-1 expression was not correlated with tumor size, stromal desmoplasia, gross classification, vascular invasion, or perineural invasion. We conclude that expression of syndecan-1 could correlate with some aspects of the biologic behaviors of ICCs and may be a useful prognostic marker.
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PMID:Reduced expression of syndecan-1 correlates with histologic dedifferentiation, lymph node metastasis, and poor prognosis in intrahepatic cholangiocarcinoma. 1456 80


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