Heregulin Drives Endocrine Resistance by Altering IL-8 Expression in ER-Positive Breast Cancer
, Ella Atlas 3,4, Travis Vander Steen 5, Elisabet Cuyàs 6,7, Sara Verdura 6,7, Ingrid Espinoza 8,9, Javier A. Menendez 6,7,* and Ruth Lupu 4,10,11,*Round 1
Reviewer 1 Report
The current study identified IL-8 as a leading cause of endocrine resistance via human cytokine antibody arrays, providing new knowledge and novel therapeutic implication towards HER2-negative breast cancer. The work can be published after minor revision.
- Figure 1B can be revised as now the first column looks like an outlier (blank between the first two is two big). Similarly, in Figure 3A and B; Another is the symbol behind ER()?
- Have the authors tested the cell viability before and after the blockade of IL-8 upon certain chemotherapeutic? This is also a piece of strong evidence to prove your conclusion.
- A discussion of the limitations and future perspectives (future studies, and applications) should also be included in section Discussion.
- Please revise your conclusion into 3-5 sentences. (the current first 3 sentences are not necessary)
Author Response
Please see the attachment
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The effect of IL-8 action in breast cancer progression was well-described.
- Supplementary information, Fig. S1 Cytokines map of the RayBio® Human Cytokine Antibody Array VII & 7.1
-> Presentation of full name of abbreviated cytokines in the footnote is necessary.
2. 2.1. Identification of IL-8 as an HRG-driven cytokine using chemokine antibody array technology
Specifically, MCF-7/pBABE control cells secreted 131 ± 14 pg IL- 8 mg protein-1, whereas MCF-7/HRG, MCF-7/HRG-M4, MCF-7/HRG-M1 cells expressed 440 ± 10, 87 ± 14, and 472 ± 19 pg IL-8 mg-1, respectively.
->Median and interquartile range would be better because of small number of included cells.
- 2.2. HRG overexpression in HER2-negative breast cancer cells qualitatively phenocopies the IL-8 cytokine signature driven by HER2 overexpression
Using the antibody-based RayBio™ Human Cytokine Array III, which simultaneously detects 42 cytokines and growth factors.
-> Please provide cytokines of RayBio™ Human Cytokine Array III in the supplementary information
- 2.2. HRG overexpression in HER2-negative breast cancer cells qualitatively phenocopies the IL-8 cytokine signature driven by HER2 overexpression
MCF-7/HRG cells, however, MCF-7/Her2-18 cells also showed an elevated secretion of TIMP-2, VEGF and GRO relative to control cells.
-> Please discuss the implication of TIMP-2, VEGF and GRO, which showed difference between MCF-7/HRG, and MCF-7/Her2-18 cells.
Author Response
Please see the attachment
Author Response File: Author Response.pdf
