Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A parallel-plate flow chamber was used to quantify the detachment of normal cloned rat embryo fibroblasts (CREF) fibroblasts, ras-transformed CREF fibroblasts (CREF T24), and CREF T24 fibroblasts transfected with a Krev/RAP1A suppressor gene (HK B1) from a confluent monolayer of normal CREF fibroblasts to determine if the expression patterns of CD44 variants (mol wt 110 and 140 kDa) corresponded with detachment properties and metastatic potential. In the detachment assay, known shear stresses ranging from 20-24 dyn/cm2 were applied to the adherent cells and the number of cells detached from the monolayer after 180 s was determined. Results showed that cellular expression of CD44 variants correlated with the metastatic potential of the cells and with the cells' ability to detach from a monolayer of normal cells. Western blot analysis showed a low level of expression of the CD44 variants in the normal cell line, CREF, and the lowly metastatic cell line, HK B1. Detachment studies showed a low percentage of detachment of both of these cell lines from a normal cell monolayer. Tumor-derived (HK B1-T) and lung nodule-derived (HK B1-M) cell lines were established and both formed tumors and metastasis with reduced latency periods as compared to HK B1, but still showed a markedly delayed latency period compared to the highly metastatic cell line, CREF T24. Both of these cell lines showed a higher expression of the CD44 variants as compared to CREF and HK B1, and detached easier than CREF and HK B1. CREF T24 showed a much higher level of expression of the variants and had a higher percentage detachment than all other cell lines. To further test the role of the CD44 variants in the ability of the cells to detach from the normal monolayer, CREF cells were transfected with a DNA construct that constitutively expresses the CD44 variants and the detachment properties of three randomly selected clones were studied. Clones 2 and 3 showed a low level of expression of the CD44 variants after transfection and detached from the normal monolayer similar to CREF. Clone 1 showed a high level of expression of the CD44 variants and the detachment of these cells was significantly higher than CREF. From these results, it is concluded that in the five cell lines studied, expression of the CD44 variants play a significant role in the ability of the cells to detach from a monolayer of normal cells. It is hypothesized that this detachment may be an important component of a cell's ability to metastasize.
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PMID:Detachment of transformed cells. Role of CD44 variants. 753 6

Knowing the differential expression of CD44 isoforms in intestinal- and diffuse-type gastric carcinomas, we used antibodies against the standard form of CD44 (CD44s) and the domain encoded by exon v6 (CD44v6) in 103 patients with primary gastric adenocarcinomas to explore the role of CD44 isoforms in metastases of both types of gastric cancer. Carcinomas of the intestinal type were more frequently CD44s and CD44v6 positive than carcinomas of the diffuse type (p = 0.034 for CD44s and p = 0.022 for CD44v6). The reactivity to these two antibodies did not correlate with histopathological and clinical prognostic factors in intestinal-type carcinoma. In contrast, expression of CD44v6 was associated with infiltrative tumor growth (p = 0.021), depth of invasion (p = 0.012), lymph node involvement (p = 0.005) and a higher incidence of distant metastasis (p = 0.069) in cancers of the diffuse type. CD44s-expressing diffuse-type tumors had a higher incidence of distant metastasis at presentation (p = 0.001), but expression of CD44s was not correlated with other clinicopathologic indices. For all cases, there was a nonsignificant association between CD44s expression and poor survival. Unexpectedly, there was also no significant difference in survival regarding expression of CD44v6 for all cases or the diffuse-type subset. This study showed the role of CD44v6 in invasion and metastases of diffuse-type gastric carcinoma and demonstrated the necessity of subclassifying tumor types when studying the clinical significance of CD44 in human cancers.
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PMID:Expression of CD44 and its clinical implication in diffuse-type and intestinal-type gastric adenocarcinomas. 753 3

Primary tumors of the central nervous system (CNS) very rarely metastasize to other parts of the body, both in animals and in man, irrespective of survival time. The only exception to this rule is observed in meningiomas in man with a metastasis incidence of 18.7%. Experimental studies have provided strong evidence for an important modulating role of the extracellular matrix upon the invasion capacity of tumors. Malignant progression of tumors depends upon accumulation of somatic mutations which impart a selective advantage for invasion into the surrounding connective stroma. Such mutations seem to result from an active confrontation and interaction between tumor cells and components of the stroma. As the parenchyma of the CNS is largely free of connective tissue no such selection interplay occurs in genuine CNS tumors, in contrast to tumors of the other parts of the body with an abundance of connective tissue surrounding them. This explains the rarity of extracranial metastases of CNS tumors. In contrast, other tumors of the body metastasize more frequently into the CNS. Obviously, this potency is correlated with the frequency of mutations at the CD44 gene locus.
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PMID:[Pathobiologic aspects of the limited extracranial metastasis capability of tumors of the central nervous system]. 754 Mar 90

Splicing variants of CD44 (CD44v) are increasingly recognised as metastasis-promoting factors in rodent and some human cancers. However, the frequency for CD44v expression in human cancers and their metastases and the status of CD44v expression in low or non-metastatic tumours is still uncertain. To address this issue, we investigated CD44 expression patterns in brain metastases (BMTs) spread from more than ten organs and five types of primary brain tumours (PBTs) by Northern blot, reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemical analysis. The results demonstrated that all of the 56 PBTs examined express standard form of CD44 (CD44s) but none of them express CD44v. In contrast, 22 of 26 BMTs studied were found with CD44v expression. Our data thus present direct evidence of a general distribution of CD44 in BMTs but suggest that such expression is an extremely rare event in PBTs. Therefore, the presence or absence of CD44v expression may be related to high or low metastatic potential of human malignancies.
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PMID:Differential CD44 expression patterns in primary brain tumours and brain metastases. 754 Dec 33

CD44 is a polymorphic family of immunologically related integral membrane glycoproteins associated with cell matrix adhesion, lymphocyte activation and targeting, and tumor growth and metastasis. We studied CD44 expression in 114 formalin-fixed paraffin-embedded thyroid tumors using the A3D8 anti-human CD44 monoclonal antibody. Sixty-five of 67 papillary carcinomas (97%) strongly expressed CD44 with an intense plasma membrane pattern. Thirty-seven of these cases originated from Albany, New York, and 30 cases from Russia. Immunoreactivity was also observed in 9 of 16 follicular adenomas (56%); 4 of 8 Hurthle cell neoplasms (50%); 5 of 15 medullary carcinomas (33%); and 3 of 8 follicular carcinomas (38%). These results show that among thyroid neoplasms, papillary carcinomas preferentially display the CD44 antigen (P < or = 0.001). Nonneoplastic follicular epithelium exhibited a low to moderate level of staining. To further characterize the CD44 isoform, we tested a subset of cases with the 2F10 anti-human CD44 variant 6 monoclonal antibody, which recognizes a CD44 variant exon (CD44v6) implicated in tumor metastasis. Eleven of 11 papillary carcinomas tested were 2F10 positive, and 1 of the follicular carcinomas was positive. These results suggest the hypothesis that deregulated CD44v6 expression on the plasma membrane of papillary carcinoma cells contributes to the ability of those cells to metastasize to regional lymph nodes and then to remain dormant for years. Our results suggest that human papillary thyroid cancer will be an interesting model in which to further study the role of CD44 isoforms, particularly those containing CD44v6, in tumor metastasis and lymphatic invasion.
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PMID:Preferential expression of the cell adhesion molecule CD44 in papillary thyroid carcinoma. 754 70

Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastasis formation in a number of different animal and human cancers. Because human cutaneous melanoma is among the most aggressive human cancers, we explored expression of CD44 isoforms (CD44v) in lesions of melanocytic tumor progression. In addition, by RT-PCR and FACS analysis we assessed CD44v RNA species and cell surface expression of CD44v in cultured melanocytes isolated from human foreskin and in a panel of 2 non-, 2 sporadically and 2 highly metastatic human melanoma cell lines. We observed that all melanocytic lesions examined showed strong uniform expression of standard CD44 (CD44s) epitopes. We did not detect CD44v6 expression in the melanocytic lesions. However, CD44 isoforms containing v5 or v10 were differentially expressed. V5 was expressed in 16%, 0%, 20%, 67% and 58% of common nevi, atypical nevi, early primary melanomas (< or = 1.5 mm), advanced primary melanomas (> 1.5 mm) and metastases, respectively, and hence was related to tumor progression. In contrast, CD44v10 was expressed in all common nevi, whereas part of the atypical nevi and most primary melanomas and metastases lacked v10. CD44v RNA patterns were closely similar in cultured melanocytes and all melanoma cell lines. Melanocytes expressed high levels of CD44s but no CD44v, whereas all melanoma cell lines expressed CD44v at the surface. Interestingly, expression of v5 was strongly increased in the highly metastatic cell lines. Our results suggest a role for CD44 variant domains, particularly v5 and v10, in human melanocytic tumor progression.
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PMID:Expression of CD44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential. 754 41

The aim of this study was to compare the distribution of CD44 variants 5 and 6 in normal mucosa and gastric cancer and to determine their relationship with histoclinical Parameters of the disease. Experimental material included 112 paraffin blocks of various human gastric carcinomas. Both variants of CD44 were detected immunohistochemically with primary antibodies deriving from Bender Med. Systems. In normal gastric mucosa positive reactions with both antibodies were observed in surface epithelium, parietal cells, myocytes and vascular endothelia. They were also found in intestinal enterocytes, esophageal epithelium and myoepithelial. Additional reactivity with antibodies against variant 6 was observed in Paneth cells. In gastric cancer, variants 5 and 6 were demonstrated in 91% and 64% of cases respectively, without significant correlation with the tumor type. The occurrence of variant 6 correlated positively with tumor size (p = 0.081) and negatively with histological grading (p = 0.093). The relationship with metastases was insignificant.
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PMID:Immunohistochemical localization of CD44 variants 5 and 6 in human gastric mucosa and gastric cancer. 754 68

The immunohistological expression of integrins and CD44 cell adhesion molecule was analyzed on neuroblastoma (NB) specimens to study the potential role of these molecules in normal differentiation and in the transformation of neural crest derivatives. None of the specimens expressed the alpha 5 beta 1 integrin heterodimer; the expression of alpha 3 beta 1 heterodimer was maintained during all stages of differentiation; alpha 1 beta 1 heterodimer was expressed on undifferentiated neuroblasts and on Schwann cells, but was lost on ganglion cells. In contrast alpha 2 beta 1, alpha 6 beta 1, alpha 6 beta 4 and alpha V beta 1 expression was usually restricted to cells differentiated in the Schwann cell lineage. Alpha V beta 3 was expressed on tumors developed in the mediastinum. CD44 was strongly detected on differentiated ganglioneuroblastomas, stage 1 and 2 ganglioneuromas, as well as low-grade stage 4S NB and normal neuroblasts migrating in the fetal adrenal gland. CD44 expression was observed on Schwann cells and ganglion cells; in contrast, it was expressed on only 50% stage 3 and 4 undifferentiated NB. None of these specimens expressed exons V5, V7 or V6. In a few specimens, an intracellular expression of exons V8-V10 was observed in ganglion cells. The expression of CD44 on NB may reflect its pattern of expression on sympatho-adrenal precursors and arrest differentiation at these stages. Conversely, CD44 expression may be silenced during malignant transformation.(ABSTRACT TRUNCATED AT 250 WORDS)
Invasion Metastasis
PMID:Expression of integrin and CD44 adhesion molecules on neuroblastoma: the relation to tumor aggressiveness and embryonic neural-crest differentiation. 754 74

CD44 designates a large family of proteins generated from one gene by alternative splicing. Variants of CD44 (CD44v) differ from the standard form (CD44s) by usage of ten variant exons in various combinations. Some variants have been causally related to the metastatic spread of rat tumor cells. In human mammary carcinomas and colorectal carcinomas, the expression of CD44v has also been correlated with more progressed tumor stages. Moreover, the expression of CD44v on mammary and colorectal carcinomas correlates with a bad prognosis for patient survival. The biochemical features of these CD44 isoforms that may account for both their normal functions and their roles in tumor progression are discussed.
Invasion Metastasis
PMID:CD44 isoforms in metastatic cancer. 754 77

The CD44 molecule and CD44 isoforms are expressed on some malignant tumours and it has been suggested that their expression may correlate with tumour spread. Human pancreatic carcinoma cell line (HPC-4) expressing CD44 was established from a patient with adenocarcinoma of pancreas. This line showed a rapid growth in vitro, several chromosome abnormalities and surface expression of some adhesion molecules (ICAM-1, LFA-3, beta 1-chain of VLA integrins, VNR). Xenotransplanted HPC-4 cells were able to grow rapidly in SCID mice as subcutaneous tumour, leading to 100% mortality within 3-5 weeks when 1 x 10(5)-1 x 10(7) cells were inoculated. Spontaneous metastases in the liver, lung, spleen and kidney of SCID mice were observed. Interestingly enough, HPC-4 cells in vivo and ex vivo also expressed HLA-DR molecules, but these were rapidly lost upon culture in vitro. It is suggested that the appearance of HLA-DR may be the result of interaction of the tumour with a local environment of the host, while CD44 expression may explain the rapid growth and occurrence of distant metastases in SCID mice. The ability of HPC-4 cells to form spontaneous metastases in SCID mice may prove to be a potentially interesting model of human carcinoma for testing new treatment modalities.
Invasion Metastasis 1995
PMID:Characterization of human pancreatic adenocarcinoma cell line with high metastatic potential in SCID mice. 754 54


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