Abstract:
:Melanoma is the most lethal skin tumor in large part because of a propensity for early metastasis. Good models of this most clinically relevant feature of melanoma are lacking. Here, we report the development of an in-vivo model of metastasis that relies on orthotopic injection of green fluorescent protein-tagged lines in immunodeficient mice, serial intravital imaging of tumor progression, and quantification of distant spread by two-photon laser scanning microscopy, immunohistochemistry, and real-time PCR analysis. Using this system, we report an assessment of the in-vivo growth and metastatic properties of 11 well-characterized human melanoma cell lines. A subset of lines showed rapid in-vivo growth with invasion of host vasculature and distant seeding of viscera in this system. The ability to form metastasis in vivo did not correlate with three-dimensional collagen invasion in vitro. Surprisingly, similar lines in terms of molecular genetic events differed markedly in their propensity to metastasize to distant organs such as brain and lung. In particular, two lines harboring B-RAF mutation and high levels of phosphorylated ERK and AKT were reproducibly unable to form tumors after orthotopic injection. Similarly, two previously identified RAS/RAF wildtype 'epithelial like' lines that do not have elevated phosphorylated ERK and AKT or express TWIST1 mRNA still showed a pronounced ability for orthotopic growth and metastatic spread. All the metastatic cell lines in this model showed increased NEDD9 expression, but NEDD9 lentiviral overexpression did not convey a metastatic phenotype on nonmetastatic cells. These data suggest that melanoma metastasis is a molecularly heterogeneous process that may not require epithelial-to-mesenchymal transition or ERK activation, although both may facilitate the process.
journal_name
Melanoma Resjournal_title
Melanoma researchauthors
Rozenberg GI,Monahan KB,Torrice C,Bear JE,Sharpless NEdoi
10.1097/CMR.0b013e328336ee17subject
Has Abstractpub_date
2010-10-01 00:00:00pages
361-71issue
5eissn
0960-8931issn
1473-5636journal_volume
20pub_type
杂志文章abstract::MicroRNAs (miRNAs) are small noncoding RNA molecules involved in gene regulation. Aberrant expression of miRNA has been associated with the development or progression of several diseases, including cancer. In a previous study, we found that the expression of miRNA-125b (miR-125b) was two-fold lower in malignant melano...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328345333b
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journal_title:Melanoma research
pub_type: 杂志文章
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abstract::Anecdotal cases of partial or complete responses have been reported after ipilimumab therapy for stage IV melanoma with brain metastasis treated earlier by surgery or radiosurgery. We report the first case of ipilimumab monotherapy resulting in durable complete remission of untreated, progressive brain metastases in a...
journal_title:Melanoma research
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doi:10.1097/CMR.0b013e3283364a37
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/01.cmr.0000195696.50390.23
更新日期:2006-02-01 00:00:00
abstract::Proteomics provides a powerful approach for screening alterations in protein expression and post-translational modification associated with particular human diseases. In this study, the analysis of protein expression was focused on malignant melanoma in order to determine the candidate genes involved in tumour progres...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200508000-00002
更新日期:2005-08-01 00:00:00
abstract::Selective sentinel lymph node (SLN) dissection is widely used in the management of cutaneous melanoma patients without clinical evidence of nodal metastases. A series of 274 consecutive melanoma patients who underwent melanoma primary excision and SLN mapping at our institutions since 1998, and were thereafter followe...
journal_title:Melanoma research
pub_type: 临床试验,杂志文章
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000420
更新日期:2018-04-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000330
更新日期:2017-06-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199808000-00008
更新日期:1998-08-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200410000-00004
更新日期:2004-10-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000281
更新日期:2016-10-01 00:00:00
abstract::Ginsenoside Rg3 is an effective chemical component extracted from the red Panix. The experiment demonstrated that it might effectively inhibit proliferation and metastasis of tumor cells. The exact molecular mechanism of Rg3 remains unclear so far. To further explore the antitumor function of Rg3, we investigated the ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32830b3536
更新日期:2008-10-01 00:00:00
abstract::For primary melanoma, there is a delay between the initial skin biopsy and sentinel lymph node dissection, which may cause anxiety for the patient. The consequences of this delay on disease progression are unknown. The goal of this study was to determine whether delay time for sentinel node dissection from the initial...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32835861f6
更新日期:2012-10-01 00:00:00
abstract::During the initiation and progression of malignant melanoma a series of genetic events accumulate, including alterations of chromosome 11q. Recently, an important tumour suppressor gene, the multiple endocrine neoplasia type 1 (MEN1) gene, has been mapped on 11q13 and has been cloned. To assess whether the MEN1 region...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199906000-00006
更新日期:1999-06-01 00:00:00
abstract::We studied the efficacy, tolerability and clinical courses of dabrafenib in patients with metastatic melanoma who were ineligible for enrolment into a clinical trial. Between July 2011 and May 2013, patients with unresectable stage III or stage IV, V600-mutated metastatic melanoma who were not eligible for inclusion i...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000036
更新日期:2014-04-01 00:00:00
abstract::The cholesterol-lowering medications, statins, inhibit cellular proliferation and induce apoptosis in an array of cancer cell lines, including melanoma. We investigated the apoptotic mechanism of lovastatin on human melanoma cell lines in vitro. The cytotoxicity of statins on multiple cell lines was examined by Cell T...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200504000-00001
更新日期:2005-04-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200404000-00006
更新日期:2004-04-01 00:00:00
abstract::Development of brain metastases despite extracerebral response to systemic immunotherapy is a common problem in melanoma patients. We have previously described a murine melanoma vaccine of interferon-gamma (IFNgamma)-treated, irradiated syngeneic B16/G3.12 and allogeneic (Cloudman) melanoma cells, plus the adjuvant DE...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200108000-00002
更新日期:2001-08-01 00:00:00
abstract::We assessed the risk of cutaneous malignant melanoma associated with the presence of ovulatory abnormalities and with the use of ovulation-inducing agents (such as clomiphene citrate) in a cohort of 3,837 women evaluated at infertility clinics in Seattle, WA, between 1974 and 1985. Computer linkage with a population-b...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199504000-00009
更新日期:1995-04-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000195
更新日期:2015-12-01 00:00:00
abstract::Protein tyrosyl phosphorylation is an essential component in intracellular signalling, with diverse and crucial functions including mediation of cell proliferation, survival, death, differentiation, migration and attachment. It is regulated by the balance between the activities of protein tyrosine kinases (PTKs) and p...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:10.1097/00008390-200010000-00001
更新日期:2000-10-01 00:00:00
abstract::Immune-checkpoint inhibitors (ICIs) exposed the oncology community to novel immune-related adverse events (irAEs). Here, we report on a retrospective analysis of patients with melanoma who developed an ICI-related, unilateral, acute and peripheral facial nerve paralysis (Bell's palsy).We retrospectively reviewed all t...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000715
更新日期:2021-01-22 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200008000-00007
更新日期:2000-08-01 00:00:00
abstract::Two human melanoma tumour cell lines, one radiation resistant and one radiation sensitive, were studied for their capacity for repair of sublethal radiation damage (SLDR) and for hyperthermia inhibition of radiation damage. The most resistant cell line demonstrated a survival curve with a large shoulder and a large SL...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199406000-00003
更新日期:1994-06-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200204000-00006
更新日期:2002-04-01 00:00:00
abstract::Our previous in vivo studies indicated that a phenolic thioether amine (PTEA), 4-S-cysteaminylphenol (CAP), selectively disintegrates melanocytes of black hair and skin, and inhibits the growth of murine and human malignant melanomas. To elucidate the mechanism of the in vivo melanocytotoxicity and anti-melanoma effec...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199211000-00002
更新日期:1992-11-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000064
更新日期:2014-06-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199510000-00002
更新日期:1995-10-01 00:00:00
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journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200308000-00003
更新日期:2003-08-01 00:00:00
abstract::Melanoma is the deadliest form of skin cancer. Ipilimumab, a novel immunotherapy, is the first treatment shown to improve survival in patients with metastatic melanoma in large randomized controlled studies. The most concerning side effects reported in clinical studies of ipilimumab fall into the category of immune-re...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32835c7e68
更新日期:2013-02-01 00:00:00