VEGF-independent novel angiogenesis factor derived from human mesothelioma cells

Article information
Progranulin and granulin-like protein as novel VEGF-independent angiogenic factors derived from human mesothelioma cells.
Eguchi R, Nakano T, Wakabayashi I.
Oncogene. 2017 Feb 2;36(5):714-722. PMID: 27345409

Overview
Malignant mesothelioma is an invasive tumour derived from the serosa of the pleura, peritoneum, pericardium, etc. Tumours of this type are resistant to most chemotherapy agents.

On the other hand, angiogenesis is essential for tumour progression, and it is known that increased angiogenesis in the lung is associated with poor prognosis of mesothelioma patients.

For this reason, monoclonal antibodies against VEGF-A, a vascular endothelial cell growth factor known to play an important role in angiogenesis, have been tested for the treatment of various tumours. However, this therapy has not led to a marked improvement in progression-free survival in patients with advanced, unresectable mesothelioma. Therefore, the following experiments were conducted to identify new angiogenic factors.

First, a culture supernatant obtained by culturing a mesothelioma cell line (NCI-H2052) in serum-free medium was added to a human vascular endothelial cell line (HUVEC) sandwiched within collagen gel or cultured in collagen gel. Dose-dependent tube formation and promotion of cell survival were observed.

Furthermore, in a similar experiment using VEGF antibody or VEGFR2 siRNA, the promotion of tube formation by the culture supernatant was shown to be VEGF independent, an observation that was consistent with clinical findings.

Culture supernatant proteins involved in angiogenesis were identified as progranulin and granulin-like protein by mass spectrometry, and these results were confirmed by experiments using granulin siRNA.

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