PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling

Round 1

Reviewer 1 Report

Thank you for being selected to revise the paper entitled: “PDGFRα enhanced infection of breast cancer cells with human cytomegalovirus but infection of fibroblasts increased pro-metastatic inflammation involving lysophosphatidate signaling”.

The presented manuscript is written in a thoughtful and understandable way. It is divided into 4 sections: introduction, results, discussion, and material and methods. In the introduction, the authors briefly characterized HCMV and the purpose of the selected research topic. This is extremely interesting considering that apart from the ability to "hijak" various processes responsible for promoting cancer, HCMV also exhibits broad immunosuppressive effects, which may ultimately have a radical impact on the tumor microenvironment. The research results are presented in 4 coherent subsections, taking into account 7 figures and the results contained in supplementary materials. In terms of content, the information was presented fairly and accurately.

My comments below regarding the manuscript are only of a technical nature:

1. The descriptions of the figures are quite long and at times they blend in with the main text. Please consider possible shortening and separation.
2. Figure 5 – in the description the last sentence is unfinished - please complete.

The authors cited and described many of the available scientific studies, focusing on the latest reports. The presented manuscript is a valuable and interesting and I recommend this article for publication in the International Journal of Molecular Sciences after minor revisions.

Author Response

Responses to Editorial comments

We thank the reviewers for critiquing the paper so efficiently. We are pleased with the complimentary comments and that the paper is acceptable with minor revisions. We have now revised the manuscript according to the following responses:

Reviewer 1

 Thank you for being selected to revise the paper entitled: “PDGFRα enhanced infection of breast cancer cells with human cytomegalovirus but infection of fibroblasts increased pro-metastatic inflammation involving lysophosphatidate signaling”.

The presented manuscript is written in a thoughtful and understandable way. It is divided into 4 sections: introduction, results, discussion, and material and methods. In the introduction, the authors briefly characterized HCMV and the purpose of the selected research topic. This is extremely interesting considering that apart from the ability to "hijak" various processes responsible for promoting cancer, HCMV also exhibits broad immunosuppressive effects, which may ultimately have a radical impact on the tumor microenvironment. The research results are presented in 4 coherent subsections, taking into account 7 figures and the results contained in supplementary materials. In terms of content, the information was presented fairly and accurately.

My comments below regarding the manuscript are only of a technical nature:

1. The descriptions of the figures are quite long and at times they blend in with the main text. Please consider possible shortening and separation.

 Response

We have tried to shorten the legend and results text as much as we think is possible without losing the essential components of the paper. We would emphasize that this was a comprehensive study intended for a high impact journal where we tried to cover all of the aspects of the work without leaving omissions. We spent a lot of time before the submission in cutting down the text and so there are few opportunities for further cuts.

However, the paper has been reformatted to provide more space between the legends and the text of the other sections and the legends shortened to address the problem of the figures blending in with the text.

1. Figure 5 – in the description the last sentence is unfinished - please complete.

Response

Done

The authors cited and described many of the available scientific studies, focusing on the latest reports. The presented manuscript is a valuable and interesting and I recommend this article for publication in the International Journal of Molecular Sciences after minor revisions.

Response

Thank you for the kind comments.

Reviewer 2 Report

Interesting study. The number of diagrams are overwhelming. Both figure texts and written results are "stuffed" and really heavy reading. I suggest to put most of the diagrams as supplementary. The text results should be shortened.

Author Response

Responses to Editorial comments

We thank the reviewers for critiquing the paper so efficiently. We are pleased with the complimentary comments and that the paper is acceptable with minor revisions. We have now revised the manuscript according to the following responses:

Reviewer 2

Interesting study. The number of diagrams are overwhelming. Both figure texts and written results are "stuffed" and really heavy reading. I suggest to put most of the diagrams as supplementary. The text results should be shortened.

Response

As described in the response to Reviewer 1, we have tried to shorten the results and figure legend texts as much as we think is possible without losing the essential components of the paper. We would emphasize that this was a comprehensive study intended for a high impact journal where we tried to cover all of the aspects of the work without leaving omissions. We already considered carefully the division of results that were put into the primary manuscript text versus the Supplementary Figures Section. Where results are significant and essential to the message of the paper, we think that these should be shown in the main manuscript text and should not be obscured by placing into the Supplementary Figure Section.  We would emphasize that this was a comprehensive study intended for a high impact journal where we tried to cover all of the aspects of the study without leaving omissions. We also spent a lot of time before the submission in cutting down the text and so there now are few opportunities for further cuts.

We hope that the reviewers will accept these responses.