Tumour progression and metastatic behaviour <i>in vivo</i> correlates with integrin expression on melanocytic tumours

Schadendorf, Dirk; Gawlik, Christian; Haney, Uwe; Ostmeier, H.; Suter, L.; Czarnetzki, Beate M.

doi:10.1002/path.1711700405

Cited by 99 publications

(76 citation statements)

References 19 publications

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“…Several studies have examined expression of the integrin family of adhesion molecules in cutaneous melanoma at various stages of tumour development. Levels of expression of different integrin subunits have been reported to increase during tumour progression, including a2,1 (Klein et al, 1991), a3 1 (Natali et al, 1993), a4pl (Schadendorf et al, 1993), a5,Bl (Danen et al, 1994), a6P1 (Natali et al, 1991) and a7 31 (Kramer et al, 1991 (Cheresh and Spiro, 1987). Thus, Albelda and colleagues (1990) noted that the ,3 subunit was only detected on VGP and metastases of cutaneous melanoma.…”

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confidence: 99%

Comparative analysis of integrins in vitro and in vivo in uveal and cutaneous melanomas

Marshall

Rutherford²,

Happerfield³

et al. 1998

Br J Cancer

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Summary Changes in integrin expression have been shown to be important for the growth and metastatic capacity of melanoma cells. In this study, we have examined the expression of av integrins by three uveal and four cutaneous malanoma lines. No lines expressed avP6 and only TXM1 3, a cutaneous line, expressed av,B8. All lines expressed avf5 and avP3 (four out of four cutaneous, two out of three uveal) or avfi1 (OM431, an uveal line). Thus, OM431 is the second uveal melanoma we have described that expresses avIl and this, we report again, functions as an alternative vitronectin/fibronectin receptor. Subcutaneous growth of cell lines in athymic mice correlated with an avp3-positive, avI1 -negative phenotype. Analysis of clinical material from cutaneous melanoma showed that although av expression was increased in 88% of metastases, this could not all be explained by up-regulation of av,B3, with only 2 out of eight skin metastases expressing this heterodimer.Using antibody SZ.21, which as we report here works in archival material, only 1 out of 15 uveal metastases expressed detectable P3. Thus, acquisition of avP3 expression, which has been implicated in cutaneous melanoma progression, may not be required for development of metastases from uveal melanoma or indeed for skin, as distinct from lymph node, metastases of cutaneous melanoma.Keywords: cell adhesion; ocular melanoma; skin melanoma Cutaneous melanoma is a tumour type whose incidence in Caucasian populations has increased dramatically over the past 80 years. The cancer generally is considered to evolve through a series of distinct pathological steps (Mastrangelo et al, 1985). Thus, melanocytic naevi progress to flat tumours that grow horizontally (radial growth phase, RGP) before they acquire the capacity to invade vertically (vertical growth phase, VGP) and then metastasize. Ocular melanomas, of which the most common are uveal melanomas, occur at about 10% the frequency of cutaneous tumours. These cancers do not seem to progress through the same stages of evolution, but the histological type of uveal melanoma determines the probable metastatic propensity. Thus, the 'spindle' forms rarely metastasize, whereas the 'epithelioid' types are highly metastatic and then usually spread preferentially to the liver (Shields and Shields, 1992).Disseminating cancer cells must interact with the extracellular matrix and this interaction is mediated principally by cell surface adhesion receptors, termed integrins (Hynes, 1992). Integrins are heterodimeric glycoproteins, consisting of a-chains non-covalently associated with ,B-chains, which are expressed at the cell surface. Several studies have examined expression of the integrin family of adhesion molecules in cutaneous melanoma at various stages of tumour development. Levels of expression of different integrin subunits have been reported to increase during tumour progression, including a2,1 (Klein et al, 1991), a3 1 (Natali et al, 1993), a4pl (Schadendorf et al, 1993), a5,Bl (Danen et al, 1994), a6P1 (Natali et al, 1991) ...

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confidence: 99%

Comparative analysis of integrins in vitro and in vivo in uveal and cutaneous melanomas

Marshall

Rutherford²,

Happerfield³

et al. 1998

Br J Cancer

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“…In interpreting our findings, several factors, particularly epidemiology of melanoma, natalizumab‐associated progressive multifocal leukoencephalopathy (PML), various aspects of the TOUCH Risk Management (RiskMAP) Action Plan, and the Safety Surveillance Program in this RiskMAP (Table 3), potential pathophysiology, and an overview of pharmacovigilance efforts for opportunistic complications of medications, should be considered 6, 7, 8, 9, 10, 11, 13, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47.…”

Section: Discussionmentioning

confidence: 99%

“…Blocking α 4 integrins on the surface of lymphocytes prevents their adhesion to vascular‐cell adhesion molecule 1 (VCAM‐1), which is expressed on the surface of vascular endothelial cells in brain and spinal cord blood vessels (the acknowledged mechanism of action for the favorable effect on MS). Studies of α 4 integrin expression show that it has different roles in melanoma 30, 31, 32, 33. The underlying pathophysiology of a potential causal relationship is uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…2) Normal melanocytes and early stage melanomas do not express α 4 integrin, whereas metastatic melanomas do 30, 31, 32, 33, 34, 35, 36. Expression of α 4 β 1 integrin shows an inverse correlation with invasive potential of an aggressive melanoma cell line (B16) 30, 33. Expression of the integrin α 4 β 1 on melanoma cells can inhibit the invasive stage of melanoma 34, 37.…”

Section: Discussionmentioning

confidence: 99%

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Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR)

et al. 2017

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A 43‐year‐old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α4 integrins. To investigate the risk‐exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab‐associated melanoma reported to regulatory agencies. Data sources included the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) (2004–2014), a FDA Advisory Committee Meeting Report, and peer‐reviewed publications. In the United States, the manufacturer maintains an FDA‐mandated Tysabri Safety Surveillance Program (part of the Tysabri Outcomes Unified Commitment to Health (TOUCH)) of natalizumab‐treated patients. We statistically compared reporting completeness for natalizumab‐associated melanoma cases in FAERs for which information was obtained entirely from the TOUCH program versus cases where FAERS information was supplemented by TOUCH program information. FAERS included 137 natalizumab‐associated melanoma reports in patients with multiple sclerosis. Median age at melanoma diagnosis was 45 years (range: 21–74 years). Changes in preexisting nevi occurred in 16%, history of cutaneous nevi occurred in 22%, diagnosis within 2 years of beginning natalizumab occurred in 34%, and 74% had primary surgical treatment. Among seven natalizumab‐treated MS patients who developed biopsy‐confirmed melanoma on treatment and reported in the literature, median age at diagnosis was 41 years (range: 38–48 years); and the melanoma diagnosis occurred following a median of 12 natalizumab doses (range: 1–77 doses). A history of mole or nevi was noted in four patients and a history of prior melanoma was noted in one patient. Completeness scores for reports were significantly lower for FAERS cases reported from the TOUCH program versus FAERS cases supplemented by TOUCH information (median score of 2 vs. 4 items out of 8‐possible items, P < 0.0007). Clinicians should monitor existing nevi and maintain suspicion for melanoma developing in natalizumab‐treated patients. The TOUCH Safety Surveillance Program, currently focused on progressive multifocal leukoencephalopathy, should be expanded to include information on other serious complications including malignancies, particularly if they are immunologic in nature.

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“…However, integrins VLA-1 and VLA-5 were dramatically unregulated in the aggressive, highly metastatic cell lines, which parallels immunohistological results on melanocytic tumours studying integrin expression during tumour progression. In those reports, VLA-1, a receptor for collagen and laminin, and VLA-5, a receptor for fibronectin, (Ruoslahti, 1991) were found to be u-regulated during malignant transformation and progression of melanocytic cells (Moratini et al, 1992;Schadendorf et al, 1993b;Danen et al, 1994). Interestingly, UKRV-Mel-2, which completely lacked any HLA-class I molecule expression on its cell surface was characterised by a poor growth rate in nude mice without development of metastases, independent of inoculation route.…”

Section: Discussionmentioning

confidence: 99%

Metastatic potential of human melanoma cells in nude mice - characterisation of phenotype, cytokine secretion and tumour-associated antigens

Schadendorf

Fichtner²,

Makki³

et al. 1996

Br J Cancer

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Tumour progression and metastatic behaviour in vivo correlates with integrin expression on melanocytic tumours

Cited by 99 publications

References 19 publications

Comparative analysis of integrins in vitro and in vivo in uveal and cutaneous melanomas

Comparative analysis of integrins in vitro and in vivo in uveal and cutaneous melanomas

Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR)

Metastatic potential of human melanoma cells in nude mice - characterisation of phenotype, cytokine secretion and tumour-associated antigens

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