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Peer-Review Record

Myeloma Microenvironmental TIMP1 Induces the Invasive Phenotype in Fibroblasts to Modulate Disease Progression

Int. J. Mol. Sci. 2023, 24(3), 2216; https://doi.org/10.3390/ijms24032216
by Rei Ishihara 1, Tsukasa Oda 2, Yuki Murakami 1, Ikuko Matsumura 3, Saki Watanabe 1, Yuta Asao 1, Yuta Masuda 1,4, Nanami Gotoh 1, Tetsuhiro Kasamatsu 1, Hisashi Takei 3, Nobuhiko Kobayashi 3, Nobuo Sasaki 2, Takayuki Saitoh 1, Hirokazu Murakami 4 and Hiroshi Handa 3,*
Reviewer 1:
Reviewer 2: Anonymous
Int. J. Mol. Sci. 2023, 24(3), 2216; https://doi.org/10.3390/ijms24032216
Submission received: 16 December 2022 / Revised: 13 January 2023 / Accepted: 18 January 2023 / Published: 22 January 2023
(This article belongs to the Section Molecular Oncology)

Round 1

Reviewer 1 Report

Congratulations on this work. 

Tumor inhibitors of metalloproteinases (TIMPs) inhibit extracellular matrix degradation and promotes fibrosis. TIMP1 has pleotropic acitivities independent of metalloproteinases.

The authors showed that TIMP-1 is produced by MM cells and not by BM stromal cells. Also, it is higher in progressive myeloma and extramedullar disease. Of interest, MMSET may control TIMP1. Furthermore, TIMP-1 plays a role in converting the phenotype of CAF. 

Author Response

Thank you for reviewing our manuscript and giving us encouragement. We really appreciate it.

Reviewer 2 Report

The manuscript by Ishihara et al provides a comprehensive review of TIMP1 role in multiple myeloma detailing the tumor microenvironment by analyzing TIMP1 expression in fibroblasts that induces disease progression. I commend the authors for performing this study, which is a valuable addition to the myeloma literature.

Author Response

Thank you for reviewing our manuscript and giving us encouragement. We really appreciate it.

Author Response File: Author Response.docx

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