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Intussusceptive angiogenesis in human metastatic malignant melanoma. : Intussusception in human melanoma

Pandita, Ankur (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Wallenberg Laboratory,Institute of Clinical Sciences, Department of Oncology
Ekstrand, Matias (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
Bjursten, Sara (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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Zhao, Zhiyuan (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Wallenberglaboratoriet,Institute of Clinical Sciences, Department of Oncology,Wallenberg Laboratory
Fogelstrand, Per, 1971 (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
Le Gal, Kristell (author)
Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Sahlgrenska Center for Cancer Research (SCCR)
Ny, Lars, 1967 (author)
Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Sahlgrenska Center for Cancer Research (SCCR),Institute of Clinical Sciences, Department of Oncology
Bergo, Martin O (author)
Karlsson, Joakim (author)
Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Sahlgrenska Center for Cancer Research (SCCR)
Nilsson, Jonas A, 1971 (author)
Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Sahlgrenska Center for Cancer Research (SCCR)
Akyürek, Levent, 1966 (author)
Levin, Malin, 1973 (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
Borén, Jan, 1963 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
Ewald, Andrew J (author)
Mostov, Keith E (author)
Levin, Max, 1969 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Clinical Sciences, Department of Oncology,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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 (creator_code:org_t)
Elsevier BV, 2021
2021
English.
In: The American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 191:11, s. 2023-2038
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Angiogenesis supplies oxygen and nutrients to growing tumors. Inhibiting angiogenesis may stop tumor growth, but vascular endothelial growth factor inhibitors have limited effect in most tumors. The limited effect may be explained by an additional, less vascular endothelial growth factor-driven, form of angiogenesis known as intussusceptive angiogenesis. The importance of intussusceptive angiogenesis in human tumors is not known. Epifluorescence and confocal microscopy was used to visualize intravascular pillars, the hallmark structure of intussusceptive angiogenesis, in tumors. Human malignant melanoma metastases, patient-derived melanoma xenografts in mice (PDX), and genetically engineered BRAF-induced, PTEN-deficient (BPT) mice (BrafCA/+Ptenf/fTyr-Cre+/0-mice) were analyzed for pillars. Gene expression in human melanoma metastases and PDXs was analyzed by RNA sequencing. Matrix metalloproteinase 9 (MMP9) protein expression and T-cell and macrophage infiltration in tumor sections were determined with multiplex immunostaining. Intravascular pillars were detected in human metastases but rarely in PDXs and not in BPT mice. The expression of MMP9 mRNA was higher in human metastases compared with PDXs. High expression of MMP9 protein as well as infiltration of macrophages and T-cell infiltration were detected in proximity to intravascular pillars. MMP inhibition blocked formation of pillars, but not tubes or tip cells, invitro. In conclusion, intussusceptive angiogenesis may contribute to the growth of human melanoma metastases. MMP inhibition blocked pillar formation invitro and should be further investigated as a potential anti-angiogenic drug target in metastatic melanoma.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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