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

Selective expression of certain chemokine receptors by melanoma cells and the presence of their ligands in tissues might govern organ site-specific metastasis. Because the expression profile of chemokine receptors in tissues of melanocytic origin is unknown, we performed a comprehensive study on melanocytic tissue samples investigating the expression of 18 chemokine receptors at the mRNA level by real-time polymerase chain reaction, using a semiquantitative approach, and of 3 chemokine receptors (CXCR6, CCR9, and XCR1) at the protein level. We report on the de novo expression of CXCR6 in primary melanomas and melanoma metastases, but absence in melanoma cell lines and congenital nevi. CXCR4 and CCR1 were the only 2 chemokine receptors that were consistently expressed in melanocytes, melanoma cell lines, primary, and metastatic melanoma; CCR1 expression increased significantly over progression. CCR9 and XCR1 transcripts were found in melanocytic lesions, and expression was confirmed by immunohistochemistry. Transcripts for CCR10 were not found in any of the lesions, but in some melanoma cell lines. Expression of CCR7 was observed in primary melanomas and some metastases. CCR5 was exclusively expressed in primary melanomas and some cutaneous metastases. Results revealed a restricted and differential pattern of chemokine receptor expression in melanoma tissue, which varies substantially from the expression profile of melanoma cell lines and warrants functional studies on some receptors.
 ...
PMID:Profiles of chemokine receptors in melanocytic lesions: de novo expression of CXCR6 in melanoma. 1730 30

Metastasis is recently the most fearsome of cancer. Pancreatic cancer is the fourth leading cause of cancer death. Morbidity and mortality from pancreatic cancer is conspicuously associated with metastasis. However, the mechanism of metastasis is not well described. Early studies mostly focus on the "soil and seed" hypothesis. Recently, the chemotaxis hypothesis has been paid more attention. Cancer cell with high expression of chemokine receptor will spread to the specific sites where the ligand is highly secreted. It has been demonstrated that SDF-1/CXCR4 signaling, one of the most important chemokine receptor-ligand complexes, was considered to play a critical role in pancreatic cancer organ-specific metastasis through some possible pathways. However, studies do not clarify the mechanism of SDF-1/CXCR4 signaling on pancreatic cancer progression. Beta-catenin, an important factor in canonical Wnt signaling pathway, also makes great contributions on cancer invasion and metastasis. It seems that Wnt/beta-catenin has a significant role in pancreatic cancer progression through interactions with different protein complexes. In the previous study of neural development, the relationship between SDF-1/CXCR4 signaling and beta-catenin has been described. It gave a clue to describe the correlation between SDF-1/CXCR4 signaling and Wnt/beta-catenin pathway. According to this, we postulate that beta-catenin is a promising key factor of SDF-1/CXCR4 signaling to regulate the metastasis of pancreatic cancer. With the stimulation of SDF-1 on highly metastatic pancreatic cancer cells, beta-catenin will separate from different complexes, translocate into the nucleus, trigger the expression of target genes and finally promote the migration of pancreatic cancer cells to specific sites. Through the observation of this crosstalk, it is possible to understand more clearly about the pancreatic cancer specific metastasis and to make some contributions on gene therapy of pancreatic cancer.
 ...
PMID:Beta-catenin is a promising key factor in the SDF-1/CXCR4 axis on metastasis of pancreatic cancer. 1737 24

Metastasis is the primary cause of death in cancer patients. However, the molecular mechanism of the metastatic process is poorly understood because it involves multiple steps with a high degree of complexity. A critical step for successful establishment of secondary colonization is the hematogenous dissemination of malignant cells. During this process, the attachment of cancer cells to the endothelial cells on microvasculature is considered to be an essential step and many adhesion molecules as well as chemokines have been found to be involved in this process. This interaction of cancer-endothelial cell is considered not only to determine the physical site of metastasis, but also to provide the necessary anchorage to facilitate tumor cell extravasation. However, recent evidence indicates that this interaction also serves as a host defense mechanism and hinders the process of metastasis. The tumor metastases suppressor gene, KAI1, has been known to block metastatic process without affecting the primary tumor growth, and this protein has been found to be able to bind to the chemokine receptor, Duffy antigen receptor for chemokines (DARC), which is expressed on endothelial cells. Importantly, this interaction markedly induces senescence of tumor cells. This novel finding is not only significant in the context of molecular dissection of metastatic process but also in the therapeutic implication to develop drugs inhibiting metastasis.
 ...
PMID:Tumor-endothelial cell interactions: therapeutic potential. 1749 48

Chemokines and their receptors play important roles in various aspects of tumoral processes, and evidence was provided for their critical involvement in determining the metastatic destination of tumor cells. Here, we analyzed in vitro and in vivo, how CCR6 expression could alter the behavior of Lewis lung carcinoma (LLC) cells, which were shown to express low levels of the CCR6 ligand, CCL20 (LARC), both in vitro and in vivo. The expression of CCR6 significantly decreased the number of metastases in immunocompetent C57BL/6 mice, without affecting the tumor-forming ability of LLC cells. This was correlated with a decrease in clonogenicity in soft and hard agar, and with increased adhesion to type-IV collagen. These two observations made in basal conditions were enhanced when CCL20 was added to the assay medium. Thus, expression of CCR6 in tumor cells, associated with the local production of CCL20, decreased the metastatic potential of the LLC line. We propose a model, in which the expression of a chemokine receptor in tumor cells can act as a metastasis-suppressor, or a metastasis-promoting factor, according to the expression, or the absence of expression of the cognate ligand(s) in the tumor.
 ...
PMID:Expression of the chemokine receptor CCR6 in the Lewis lung carcinoma (LLC) cell line reduces its metastatic potential in vivo. 1759 91

To study the role of the chemokine receptor CCR7 in the metastatic process, a murine CCR7 gene was transduced in two mammary cancer cell lines with different origins and molecular features; TS/A, derived from a spontaneous mammary cancer of BALB/c strain, and N202.1A, derived from a HER-2/neu transgenic mammary cancer (FVB background) and characterized by a high expression of HER-2/neu. Transduced CCR7 conferred to mammary cancer cells a chemotactic response towards CCL21 (a CCR7 ligand), but did not consistently affect in vitro growth properties. In vivo, CCR7-engineered cells gave rise to tumors in syngeneic hosts with growth rates similar to or slightly lower than the controls and with similar patterns of spontaneous metastases. When injected directly intravenously to study the late post-intravasation phases of metastasis, CCR7-engineered cells showed a strongly decreased lung colonizing ability. Such an effect was observed both with HER-2/neu-positive and -negative mammary cancer cells. When used as a prophylactic vaccine, CCR7-transduced cell vaccine succeeded in the long-term control of mammary tumorigenesis in 25% of the HER-2/neu transgenic females, suggesting an increased immunogenicity of CCR7-engineered cells.
 ...
PMID:Expression of a functional CCR7 chemokine receptor inhibits the post-intravasation steps of metastasis in malignant murine mammary cancer cells. 1761 70

Expression of chemokine receptors by tumors, specifically CCR4 on cutaneous T cell lymphomas, is often associated with a poor disease outcome. To test the hypothesis that chemokine receptor-expressing tumors can be successfully controlled by delivering toxins through their chemokine receptors, we have generated fusion proteins designated chemotoxins: chemokines fused with toxic moieties that are nontoxic unless delivered into the cell cytosol. We demonstrate that chemokines fused with human RNase eosinophil-derived neurotoxin or with a truncated fragment of Pseudomonas exotoxin 38 are able to specifically kill tumors in vitro upon internalization through their respective chemokine receptors. Moreover, treatment with the thymus and activation-regulated chemokine (CCL17)-expressing chemotoxin efficiently eradicated CCR4-expressing cutaneous T cell lymphoma/leukemia established in NOD-SCID mice. Taken together, this work represents a novel concept that may allow control of growth and dissemination of tumors that use chemokine receptors to metastasize and circumvent immunosurveillance.
 ...
PMID:CCR4-expressing T cell tumors can be specifically controlled via delivery of toxins to chemokine receptors. 1764 Oct 67

Cancer metastasis results from a non-random process, in which organ selectivity by the tumor cells is largely determined by factors that are expressed at the remote organs that eventually turn into preferred sites of metastasis formation. These factors support the consecutive steps required for metastasis formation, including tumor cell adhesion to microvessel walls, extravasation into target tissue and migration. Of the different components that regulate organ selectivity, instrumental roles were recently attributed to chemokines and their receptors. The present review presents the rationale standing behind the first studies looking at the potential involvement of chemokine-related components in organ selectivity. Based on these studies and many others that followed, the current paradigm is that chemokines that are expressed at specific organs determine to large extent organ specificity by promoting tumor cell adhesion to microvessel walls, by facilitating processes of extravasation into the target tissue and by inducing tumor cell migration. Moreover, chemokines can possibly support additional steps that are required for "successful" establishment of metastases, such as tumor cell proliferation and survival. The review focuses on the CXCL12-CXCR4 pair as the role model in our current understanding of chemokine involvement in organ selectivity. This review also describes the prominent roles played by CCR7 and its corresponding chemokine ligands (CCL21, CCL19) in lymph node metastasis, and of the CCR10-CCL27 axis in melanoma skin survival and metastasis. Overall, the present discussion describes chemokines as important constituents of the tumor microenvironment at metastatic sites, dictating directionality of chemokine receptor-expressing tumor cells, facilitating their adhesion and extravasation, and eventually contributing to organ selectivity.
Clin Exp Metastasis 2008
PMID:Organ selectivity in metastasis: regulation by chemokines and their receptors. 1789 5

The chemotactic cytokines called chemokines are a superfamily of small secreted cytokines that were initially characterized through their ability to prompt the migration of leukocytes. Attention has been focused on the chemokine receptors expressed on cancer cells because cancer cell migration and metastasis show similarities to leukocyte trafficking. CXC chemokine receptor 4 (CXCR4) was first investigated as a chemokine receptor that is associated with lung metastasis of breast cancers. Recently, CXCR4 was reported to be a key molecule in the formation of peritoneal carcinomatosis in gastric cancer. In the present review, we highlight current knowledge about the role of CXCR4 in cancer metastases. In contrast to chemokine receptors expressed on cancer cells, little is known about the roles of cancer cell-derived chemokines. Cancer tissue consists of both cancer cells and various stromal cells, and leukocytes that infiltrate into cancer are of particular importance in cancer progression. Although colorectal cancer invasion is regulated by the chemokine CCL9-induced infiltration of immature myeloid cells into cancer, high-level expression of cancer cell-derived chemokine CXCL16 increases infiltrating CD8(+) and CD4(+) T cells into cancer tissues, and correlates with a good prognosis. We discuss the conflicting biological effects of cancer cell-derived chemokines on cancer progression, using CCL9 and CXCL16 as examples.
 ...
PMID:Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response. 1789 51

Multiple myeloma (MM) is a malignant B-cell disorder characterized by a monoclonal expansion of plasma cells (PC) in the bone marrow (BM). During the main course of disease evolution, MM cells depend on the BM microenvironment for their growth and survival. Reciprocal interactions between MM cells and the BM mediate not only MM cell growth, but also protect them against apoptosis and cause bone disease and angiogenesis. A striking feature of MM represents the predominant localization and retention of MM cells in the BM. Although BM PC indeed represent the main neoplastic cell type, small numbers of MM cells can also be detected in the peripheral blood circulation. It can be assumed that these circulating cells represent the tumour-spreading component of the disease. This implicates that MM cells have the capacity to (re)circulate, to extravasate and to migrate to the BM (homing). In analogy to the migration and homing of normal leucocytes, the BM homing of MM cells is mediated by a multistep process of extravasation with adhesion to the endothelium, invasion of the subendothelial basement membrane, followed by further migration within the stroma, mediated by chemotactic factors. At the end stage of disease, MM cells are thought to develop autocrine growth supporting loops that enable them to survive and proliferate in the absence of the BM microenvironment and to become stroma-independent. In this stage, the number of circulating cells increases and growth at extramedullary sites can occur, associated with alteration in adhesion molecule and chemokine receptor expression. This review summarizes the recent progress in the study of the extravasation and homing mechanisms of MM cells.
Clin Exp Metastasis 2008
PMID:Extravasation and homing mechanisms in multiple myeloma. 1795 14

Cruciferous vegetables are thought to protect against numerous types of cancer. 3,3'-Diindolylmethane (DIM) is an acid-catalyzed product generated during the consumption of cruciferous vegetables and appears to be chemoprotective for breast cancer. The interaction between the chemokine receptor, CXCR4, and its unique ligand, CXCL12, is known to mediate the progression and metastasis of breast and other cancers. Organs to which these cancers metastasize secrete CXCL12, which binds to CXCR4 expressed on the surface of primary cancer cells. This process subsequently stimulates the invasive properties of the cancer cells and attracts them to the preferred organ sites of metastases. We have found that DIM down-regulates both CXCR4 and CXCL12 in MCF-7 and MDA-MB-231 breast cancer cells as well as in BG-1 ovarian cancer cells at the transcriptional level and in an estrogen-independent manner. We demonstrate that the potential of MDA-MB-231 and BG-1 cells for chemotaxis and invasion towards CXCL12, but not towards IL-6 or fetal bovine serum, respectively, is inhibited by DIM. Furthermore, we show that DIM down-regulates CXCR4 under hypoxia and CXCL12 under estradiol-inducing conditions. Our data suggest that one mechanism whereby DIM protects against breast, ovarian, and possibly other cancers is through the repression of CXCR4 and/or CXCL12, thereby lowering the invasive and metastatic potential of these cells.
 ...
PMID:CXCR4 and CXCL12 down-regulation: a novel mechanism for the chemoprotection of 3,3'-diindolylmethane for breast and ovarian cancers. 1837 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>