Ultrastructural and immunohistochemical studies of the periendothelial matrix in human melanoma: evidence for an amorphous matrix containing laminin

Lugassy, Claire; Dickersin, G. Richard; Christensen, Lise; Karaoli, Themis; LeCharpentier, M.; Escande, Jean-Paul; Barnhill, R. L.

doi:10.1111/j.1600-0560.1999.tb01806.x

Cited by 46 publications

(31 citation statements)

References 24 publications

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“…8,9 The spread of tumor cells via EVMM was proposed based upon ultrastructural and immunohistochemical stains that demonstrated the close approximation of melanoma cells to blood vessel endothelial cells, in a pericytic location. [48][49][50] It has been shown that melanoma cells are separated from endothelial cells by an amorphous matrix containing 'free' laminin, which is not incorporated into the basement membrane, forming an 'angio-tumoral complex'. 48,49,51 The presence of the C16 laminin peptide increases the distance of angiotropic migration of melanoma cells in vitro.…”

Section: Extravascular Migratory Metastasis and Angiotropismmentioning

confidence: 99%

“…[48][49][50] It has been shown that melanoma cells are separated from endothelial cells by an amorphous matrix containing 'free' laminin, which is not incorporated into the basement membrane, forming an 'angio-tumoral complex'. 48,49,51 The presence of the C16 laminin peptide increases the distance of angiotropic migration of melanoma cells in vitro. 52 Furthermore, ex vivo and in vivo studies with time-lapse video microscopy have documented the migration of melanoma cells along the abluminal surface of vascular channels without blood vessel invasion, arguing against angiotropism just representing an early stage in the vascular invasion process.…”

Section: Extravascular Migratory Metastasis and Angiotropismmentioning

confidence: 99%

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Lymphatic invasion and angiotropism in primary cutaneous melanoma

Moy

Duncan

Kraft

2017

Laboratory Investigation

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Access of melanoma cells to the cutaneous vasculature either via lymphatic invasion or angiotropism is a proposed mechanism for metastasis. Lymphatic invasion is believed to be a mechanism by which melanoma cells can disseminate to regional lymph nodes and to distant sites and may be predictive of adverse outcomes. Although it can be detected on hematoxylin-and eosin-stained sections, sensitivity is markedly improved by immunohistochemistry for lymphatic endothelial cells. Multiple studies have reported a significant association between the presence of lymphatic invasion and sentinel lymph node metastasis and survival. More recently, extravascular migratory metastasis has been suggested as another means by which melanoma cells can spread. Angiotropism, the histopathologic correlate of extravascular migratory metastasis, has also been associated with melanoma metastasis and disease recurrence. Although lymphatic invasion and angiotropism are not currently part of routine melanoma reporting, the detection of these attributes using ancillary immunohistochemical stains may be useful in therapeutic planning for patients with melanoma.

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Section: Extravascular Migratory Metastasis and Angiotropismmentioning

confidence: 99%

Section: Extravascular Migratory Metastasis and Angiotropismmentioning

confidence: 99%

Lymphatic invasion and angiotropism in primary cutaneous melanoma

Moy

Duncan

Kraft

2017

Laboratory Investigation

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“…Although the surrounding tissue is typically matrix rich, the nests are almost entirely cellular with only small fragments of basement membrane proteins and fibronectin, and overall very low ECM compared with normal melanocytes or hyperplastic nevi (7,8). The high production of active proteases, both metalloproteinases and components of the plasmin system, probably contributes to the minimal ECM present within these tumors (9,10).…”

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confidence: 99%

Integrin Agonists as Adjuvants in Chemotherapy for Melanoma

Schwartz

McRoberts²,

Coyner³

et al. 2008

Clinical Cancer Research

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Purpose: Metastatic melanomas are generally resistant to chemotherapy and radiation, even when wild-type for p53. These tumors often grow in small nests where many of the cells have little contact with extracellular matrix (ECM). Previous work showed that M21melanomas undergo apoptosis in response to chemotherapy when cells are adherent to ECM but not in suspension. Thus, reduced integrin-dependent adhesion to ECM could mediate therapy resistance. The goal of this study was to test whether stimulation of integrin signaling could increase chemotherapeutic efficacy. Experimental Design: Colony forming assays and survival assays were used to test the responses of melanoma lines in vitro. Severe combined immunodeficient mice with subcutaneous human melanomas received chemotherapy with or without reagents that stimulate integrin signaling; tumor volume was then monitored over time. Results: Clonal growth assays confirmed that M21 cells showed reduced sensitivity to the chemotherapeutic drug 1-h-D-arabinofuranosylcytosine (araC). When five additional primary melanoma lines were screened, 80% showed higher sensitivity when adherent compared with suspended. Subcutaneous M21 tumors in vivo showed minimal ECM between tumor cells. To evaluate the importance of integrin signaling in chemoresistance in this model, mice were treated with araC, with or without the multivalent snake venom disintegrin contortrostatin or the activating anti-h1 integrin antibody TS2/16. Although araC, TS2/16, or contortrostatin alone had little effect on M21 tumor growth, combining araC with either integrin signaling reagents strongly reduced growth (P = 0001). Conclusions: Loss of integrin-mediated adhesion is rate limiting for therapeutic response in this model. Combining chemotherapy with reagents that stimulate integrin signaling may therefore provide a new approach to therapy.Melanomas are usually resistant to chemotherapy and radiation even at early stages (1). Surgery is therefore the major mode of treatment, which, if unsuccessful, leaves few options. As a consequence, 5-year survival rates for patients with unresectable or metastatic disease are <10% (2). Because melanomas often have wild-type p53 genes and lack known defects in other DNA damage and apoptosis pathways, the reasons for chemotherapy resistance are poorly understood.Integrin-mediated adhesion promotes the transmission of many signaling pathways initiated by growth factor receptors, including Erk mitogen-activated protein kinase, phosphatidylinositol-3-OH-kinase, and Rho family GTPases (3). As a result of these synergies, many cell types require integrin-mediated adhesion to extracellular matrix (ECM) for survival (4). This mechanism, however, is generally lost in metastatic cancers. Among cells that survive well in suspension, a subset exhibits a synergy between adhesion and DNA damage pathways (5, 6). These include mouse embryo fibroblasts, human fibrosarcoma, and human melanoma. In these systems, including melanomas, loss of adhesion results in decreased p53 level...

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“…Lugassy et al first described the pericyte-like position of invading melanoma cells along the blood vessel basal lamina [32][33][34] . In fact, 91% of cases of human melanoma reviewed in another study did not have a clearly defined basement membrane [35] . Building on these findings, human melanoma cells were shown to localize to both endothelial tubules formed in vitro as well as invade in a perivascular fashion when injected ex vivo into the brains of mice [6,36] .…”

Section: Pericyte Mimicry / Extravascular Migratory Metastasismentioning

confidence: 96%

Review of Pericytes in Tumor Biology

Scott¹,

Jia²,

Lam³

et al. 2015

International Journal of Orthopaedics

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Pericytes are contractile cells that surround the endothelium of capillaries and venules throughout the body. Pericytes were once thought to have a limited role in blood pressure control and angiogenesis. Today, knowledge about pericytes and other perivascular stem cells has vastly expanded. The understanding of the biologic significance of pericytes was most changed by the recognition of the perivascular identity of mesenchymal stem cells. The following review article will summarize the known functions and importance of pericytes in particular relevance to tumor biology. These roles include: (1) pericytes as the potential cell of origin for multiple soft tissue tumors; (2) the role of pericyte in regulating tumor cell vascular invasion; and 3) angiotropism or 'pericytic mimicry' as a mechanism of malignant tumor spread. Although not discussed, the role of pericytes in pathophysiology far exceeds the realms of tumor biology, including cardiovascular atherosclerotic disease, chronic kidney disease, fibrotic repair processes, and fibroproliferative diseases. In summary, the known roles of pericytes in tumor formation, growth, and invasion have greatly expanded. These include pericytic differentiation in soft tissue tumors, regulation of vascular invasion in solid tumors, and extravascular migratory migration of common malignancies.

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Ultrastructural and immunohistochemical studies of the periendothelial matrix in human melanoma: evidence for an amorphous matrix containing laminin

Cited by 46 publications

References 24 publications

Lymphatic invasion and angiotropism in primary cutaneous melanoma

Lymphatic invasion and angiotropism in primary cutaneous melanoma

Integrin Agonists as Adjuvants in Chemotherapy for Melanoma

Review of Pericytes in Tumor Biology

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