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Updated: Jun 12, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET
Diala El Khoury1, Damien Destouches, Renée Lengagne
1Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), 27 rue du Faubourg Saint-Jacques, 75014 Paris, France.
Background:
The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity.
Methods:
The in vivo antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse.
Results:
HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-alpha in the TIII cells and in melanoma tumors of RET mice.
Conclusions:
Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or as an adjuvant therapy in association with current therapeutic interventions on a virulent cancer like melanoma.
Insights
The HB-19 pseudopeptide delayed melanoma onset and reduced metastasis in mice without toxicity. This nucleolin antagonist shows promise as a novel therapeutic for virulent cancers like melanoma.
Area of Science:
- Oncology
- Cancer Biology
- Drug Discovery
Background:
- Cell-surface nucleolin is crucial in cancer, with its ligands impacting tumorigenesis and angiogenesis.
- The HB-19 pseudopeptide, a nucleolin antagonist, previously suppressed human breast tumor xenografts without toxicity.
- This study investigates HB-19's efficacy against spontaneous melanoma development.
Purpose of the Study:
- To evaluate the in vivo antitumoral action of HB-19 on spontaneous melanoma in RET transgenic mice.
- To explore the molecular mechanisms underlying HB-19's effects on melanoma cells.
Main Methods:
- HB-19 was administered prophylactically to young RET mice for 300 days.
- Melanoma cell line (TIII) derived from RET mice was used for molecular studies.
- Tumor onset, frequency, metastasis, and microvessel density were assessed in treated and control mice.
Main Results:
- HB-19 treatment significantly delayed melanoma onset and reduced tumor frequency and visceral metastasis.
- No toxicity was observed in normal tissues.
- HB-19 restored contact inhibition, impaired anchorage-independent growth, and downregulated key genes (MMP-2, MMP-9, TNF-α) in melanoma cells and tumors.
Conclusions:
- HB-19 did not prevent melanoma development but significantly delayed tumor onset and inhibited metastasis.
- HB-19 demonstrates potential as a standalone or adjuvant therapy for melanoma.
- Further research into HB-19 as a therapeutic agent for virulent cancers is warranted.
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