Anti-tumor effects of the peptide TMTP1-GG-D(KLAKLAK)(2) on highly metastatic cancers
Authors: Liangsheng Fan
Shuhong Yang
Wanhua Yang
Ling Xi
Yan Liu
Xiangyi Ma
Shixuan Wang
Shu Li
Danfeng Luo
Shuangmei Ye
Jianfeng Zhou
Ronghua Liu
Ding Ma
Li Meng
Journal: PloS one (2012)
Discipline: Multidisciplinary
Keywords: cancer treatment; peptide; metastatic tumors; apoptosis; antimicrobial peptide
Affiliations: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.

Abstract:  The treatment of cancer such as oligonucleotides or peptides requires efficient delivery systems. A novel peptide, TMTP1, previously derived and identified in our laboratory showed remarkable ability to target highly metastatic tumors both in vitro and in vivo, even at the early stage of occult metastasis foci. TMTP1 moderately inhibited tumor cell viability, although not enough to deem it an efficient killer of tumor cells. In this study, we sought to enhance the anti-tumor activity of TMTP1. To do this, we fused it to an antimicrobial peptide, (D)(KLAKLAK)(2), and termed the resulting peptide TMTP1-DKK. We found that TMTP1-DKK could trigger rapid apoptosis in human prostate and gastric cancer cells through both the mitochondrial-induced apoptosis pathway and the death receptor pathway. Furthermore, direct injection of TMTP1-DKK into mice with prostate and gastric xenograft cancers resulted in reduction of tumor volumes and a significant delay in tumor progression and metastasis in vivo. These results suggest that TMTP1-DKK may serve as a powerful therapeutic agent for metastatic tumors. 

Retracted: No

PubPeer comments:
 Concern about Figure 2F, from a group with papers with other problematic images. The PC-3M-1E8 control panel appears to contain an area that is also visible in the PC-3M-1E8 svTMTP1-DKK panel, as highlighted with red boxes. ![file] , 
 2020 Expression of Concern. https: journals.plos.org plosone article?id=10.1371 journal.pone.0231923 After the publication of this article [1], the authors notified the journal office of an error in an image panel in Fig 2F; further concerns were identified in Fig 4A during editorial follow up. Specifically: In Fig 2F, the image panel representing PC-3M-1E8 cells treated with 10 u03bcM svTMTP1-DKK is incorrect, and shares a region of overlap with the panel representing PC-3M-1E8 control cells. In Fig 4A, there is a region of overlap between the PC-3M-1E8 control panel and the PC-3M-1E8 TMTP1-DKK panel. The authors indicated that there was an error in the preparation of the figures, and that this does not affect the results and conclusions of the article. They also indicated that the original data underlying the published figures are no longer available, and they have provided results from repeat experiments for Figs 2 and 4, available via this notice as Supporting Information (S1 File, the underlying data from the repeat experiments is included as S2 File, S3 File). The cell survival rates in the repeat experiments were determined by CCK8 assays, as opposed to MMT assays used for the original Fig 2. The authors have indicated this change in methodology is due to the high sensitivity and colour stability of CCK8 assays for detecting cell proliferation Additional information regarding the mouse experimental techniques have been provided by the authors as follows: For assessment of survival, mice were sacrificed when tumors grew to a diameter of 2.0 cm (or 4.2 cm3) or when it was observed that an animal was in poor physical condition. The animals were monitored at least twice weekly. Endpoints for the survival study were based on the following: A body condition score of 1 5 based on scoring system from u201c1u201d (emaciated wasted) to u201c5u201d (obese). A body condition score of 2 5 and the animal displayed a profoundly lethargic state (significantly decreased activity responsiveness). The tumor affected the animalu2019s gait or normal posture, ability to eat, urinate, or defecate independent of tumor size. The PLOS ONE Editors issue this Expression of Concern to alert readers to the errors in Figs 2 and 4, and to the concerns about the reliability of the images in those figures. References 1.Ma X, Xi L, Luo D, Liu R, Li S, Liu Y, et al. (2012) Anti-Tumor Effects of the Peptide TMTP1-GG-D(KLAKLAK)2 on Highly Metastatic Cancers. PLoS ONE 7(9): e42685. https: doi.org 10.1371 journal.pone.0042685https: doi.org 10.1371 journal.pone.0042685 , 
 Here s an illustration of the issue in 4A. *** ![file] ,