Page 71 - GPD-2-4

Gene & Protein in Disease Topical Me-EGF application in melanoma tumor growth

skin, while relatively high percentage of HER2/HER3 China (VGHNSU109-004, VGHNSU111-008, and
co-expression or triple expression of EGFR/HER2/HER3 KSVNSU110-005).
can be detected in basal cell carcinomas and squamous cell
carcinomas compared to normal skin . An ONCOMINE Conflict of interest
[27]
database analysis shows a higher RNA expression of HER3 The authors have declared no conflicts of interest.
in cutaneous melanoma than in normal skin tissues,
and under-expression of EGFR and HER2 in cutaneous Author contributions
melanoma, with EGFR displaying the lowest expression.
There is, however, no significant difference in HER4 Conceptualization: Chien-Shan Wu, Ming-Hong Tai
expression between cutaneous melanoma and normal skin Formal analysis: Chi-Fang Wu, Yi-Tzu Li
tissues . In addition, targeting HER2 by pharmacologic Investigation: Jian-Ching Wu, Ching-Min Tseng, Le-Shin
[28]
inhibitor is beneficial to the suppression of melanoma cell Chang, Yi-Wen Li
invasiveness and growth [29,30] . Taken together, these studies Writing – original draft: Jian-Ching Wu
indicate that HER2 and HER3 play a more important role Writing – reviewing & editing: Ming-Hong Tai, Jian-Ching Wu
in melanoma development. The present study showed that All co-authors reviewed and approved the final manuscript.
Me-EGF application is able to increase the phosphorylated
and total EGFR protein levels in B16-F10 melanoma cells, Ethics approval and consent to participate
although the ratio of phosphorylated EGFR to total EGFR All animal procedures in this study were approved by
protein does not achieve statistically significant difference. Animal Care and Use Committee (IACUC) of National
Nevertheless, Me-EGF application does not contribute to Sun Yat-sen University (approval ID: 11128).
the activation of phosphorylated and total HER2 proteins
in melanoma cells. Thus, these results indicated that the Consent for publication
administration of Me-EGF might not trigger HER2-
mediated oncogenic signaling pathway. On the other hand, Not applicable.
some clinical studies have shown that treating patients with Availability of data
recombinant EGF protein did not increase the incidence
of cancer [31,32] . Further studies should be conducted to The data that support the findings of this study are available
investigate whether other ErbB family members, especially from the corresponding author upon reasonable request.
HER3, are activated in Me-EGF-treated melanoma cells.

We acknowledge several limitations in this study. First, References
the topical application of Me-EGF, which is prepared as 1. Yao Q, Yu Z, Liu P, et al., 2019, High efficient expression and
liquid-based formulation, posed some challenges in terms purification of human epidermal growth factor in Arachis
of absorption and penetration, affecting drug adhesion to Hypogaea L. Int J Mol Sci, 20(8): 2045.
the skin surface of mice. Second, the B16-10 melanoma https://doi.org/10.3390/ijms20082045
mouse model may not fully recapitulate the clinical and 2. Gurtner GC, Werner S, Barrandon Y, et al., 2008, Wound
genetic features of human melanoma. Future experiments repair and regeneration. Nature, 453(7193): 314–321.
are warranted to overcome the above-mentioned
shortcomings. https://doi.org/10.1038/nature07039
3. Werner S, Grose R, 2003, Regulation of wound healing by
5. Conclusion growth factors and cytokines. Physiol Rev, 83(3): 835–870.
Topical Me-EGF application does not promote melanoma https://doi.org/10.1152/physrev.2003.83.3.835
tumor growth in vitro and in vivo. 4. Tiaka EK, Papanas N, Manolakis AC, et al., 2012, Epidermal
Acknowledgments growth factor in the treatment of diabetic foot ulcers: An
update. Perspect Vasc Surg Endovasc Ther, 24(1): 37–44.
®
The study agent, Me-rhEGF (NewEpi ), was a generous gift https://doi.org/10.1177/1531003512442093
given by JoyCom Bio-chem Co. Ltd., Kaohsiung, Taiwan,
Republic of China. 5. Hardwicke J, Schmaljohann D, Boyce D, et al., 2008,
Epidermal growth factor therapy and wound healing--past,
Funding present and future perspectives. Surgeon, 6(3): 172–177.

This work was supported by grants funded by Kaohsiung https://doi.org/10.1016/s1479-666x(08)80114-x
Veterans General Hospital, Taiwan, Republic of 6. Mao S, Sun W, Kissel T, 2010, Chitosan-based formulations

Volume 2 Issue 4 (2023) 7 https://doi.org/10.36922/gpd.1848