Abstract:
:Metastasis remains the major cause of therapeutic failure, poor prognosis and high mortality in breast and prostate cancer patients. Aberrant microenvironments including hypoxia and acidic pH are common features of most solid tumors that have been long associated with enhanced metastasis and poor patient outcomes. Novel approaches to reduce metastatic incidences and improve overall survival of cancer patients clearly are needed. The crucial role of Cathepsin L (CTSL) in the dissemination of tumor cells has led to the development of novel cathepsin L inhibition strategies. The present study evaluated the ability of KGP94, a small molecule inhibitor of CTSL, to impair the metastatic phenotype of prostate (PC-3ML) and breast (MDA-MB-231) cancer cells both under normal and aberrant microenvironmental conditions. To assess the role of CTSL in hypoxia and acidosis triggered metastasis associated cell functions, secreted CTSL levels were determined under conditions pertinent to the tumor microenvironment. Acute exposures to hypoxic or acidic conditions significantly elevated secreted CTSL levels either through an increase in intracellular CTSL levels or through activation of lysosomal exocytosis or both, depending on the tumor type. Increases in CTSL secretion closely paralleled enhanced tumor cell migration and invasion suggesting that CTSL could be an essential factor in tumor microenvironment triggered metastasis. Importantly, KGP94 treatment led to marked attenuation of tumor cell invasion and migration under both normal and aberrant microenvironmental conditions suggesting that it may have significant utility as an anti-metastatic agent.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Sudhan DR,Siemann DWdoi
10.1007/s10585-013-9590-9subject
Has Abstractpub_date
2013-10-01 00:00:00pages
891-902issue
7eissn
0262-0898issn
1573-7276journal_volume
30pub_type
杂志文章abstract::Previous studies have shown that thrombospondin (TSP) is an adhesion factor for some human tumor cells. The previous studies have shown further that tumor cells which utilize TSP as an adhesion factor also synthesize it. This study continues the effort to understand how TSP production and expression are regulated in h...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01753679
更新日期:1989-05-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00880070
更新日期:1993-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-005-8186-4
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-016-9798-6
更新日期:2016-08-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00114976
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-016-9809-7
更新日期:2016-10-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006509312674
更新日期:1998-05-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,多中心研究
doi:10.1007/s10585-014-9685-y
更新日期:2015-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9132-4
更新日期:2008-01-01 00:00:00
abstract::The growth of metastatic prostate cancer cells in the bone involves an intimate interaction between the tumor cells and various elements of the bone microenvironment, resulting in increased rate of bone turnover and rapid tumor growth. The alpha(v)beta3 integrin has been shown to play an important role in tumor growth...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1025461507027
更新日期:2003-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-005-6244-6
更新日期:2005-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-020-10040-4
更新日期:2020-08-01 00:00:00
abstract::The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) to modify integrin expression and adhesive functions of tumor cells in vitro and to examine corresponding metastatic effects in vivo. Preincubation of HT-29 cells with 100 U/ml of I...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00121213
更新日期:1996-03-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01784377
更新日期:1988-11-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-016-9800-3
更新日期:2016-08-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9059-9
更新日期:2007-01-01 00:00:00
abstract::About 30-40% of patients with renal cell carcinoma (RCC) will develop metastasis after curative nephrectomy. There is a strong need to identify the early metastasis with conventional and molecular risk factors. The present study aimed to test if analysis of the CA9 gene can provide useful information to predict early ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9064-z
更新日期:2007-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1021322201816
更新日期:2002-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006567229929
更新日期:1998-10-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1026553414492
更新日期:2000-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006540824969
更新日期:1998-04-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-019-10016-z
更新日期:2020-04-01 00:00:00
abstract::To elucidate the development of bone metastasis in human neuroblastoma, bone marrow and bone metastases were analysed histologically in a hematogeneous metastasis model of murine neuroblastoma. The bone marrow metastasis occurred initially in the bone marrow sinusoid where tumor cells adhered and extravasated to bone ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00128962
更新日期:1996-10-01 00:00:00
abstract:BACKGROUND:Metastasis to bone from endometrial adenocarcinoma is rare, when metastasises it usually locates in axial skeleton. Metastasis to extremities is extremely rare. Additionally the detection of the bone metastasis as a presenting feature is uncommon. In the present study we report the 10th cases of bone metasta...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9061-2
更新日期:2007-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,多中心研究,评审
doi:10.1007/s10585-012-9503-3
更新日期:2012-10-01 00:00:00
abstract::We have previously reported that induction of MMP-2 activation by Concanavalin A (ConA) in MDA-MB-231 human breast cancer cells involves both transcriptional and post-transcriptional mechanisms, and that the continuous presence of ConA is required for MMP-2 activation (Yu et al. Cancer Res, 55, 3272-7, 1995). In an ef...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006580406314
更新日期:1998-02-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-011-9403-y
更新日期:2011-12-01 00:00:00
abstract::The purpose of this study was to identify possible alterations in proto-oncogenes (c-fos, c-jun, c-erbB1, c-erbB2 and c-myc) at the protein level in primary lung carcinomas and simultaneous metastatic lymph nodes of 21 patients. The analysis showed that proteins of c-jun and c-myc were expressed in a significantly hig...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01753840
更新日期:1994-07-01 00:00:00