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Biological Sex Differences of Fibrosis During the Development of Cancer Cachexia
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  • Tyrone Washington,
  • Eleanor R. Schrems,
  • Wesley S. Haynie,
  • Megan Rosa-Caldwell,
  • Jacob Brown,
  • Landen Saling,
  • Seongkyun Lim,
  • Richard Perry,
  • Lemuel A. Brown,
  • David Lee,
  • Nicholas Greene
Tyrone Washington
University of Arkansas Fayetteville

Corresponding Author:tawashin@uark.edu

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Eleanor R. Schrems
University of Arkansas Fayetteville
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Wesley S. Haynie
University of Arkansas Fayetteville
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Megan Rosa-Caldwell
University of Arkansas Fayetteville
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Jacob Brown
University of Arkansas Fayetteville
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Landen Saling
University of Arkansas Fayetteville
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Seongkyun Lim
University of Arkansas Fayetteville
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Richard Perry
University of Arkansas Fayetteville
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Lemuel A. Brown
University of Arkansas Fayetteville
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David Lee
University of Arkansas Fayetteville
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Nicholas Greene
University of Arkansas Fayetteville
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Abstract

AIM Cachexia is characterized by losses in lean body mass and its progression results in worsened quality of life and exacerbated outcomes in cancer patients. However, the role and impact of fibrosis during the early stages and development of cachexia in under-investigated. The purpose of this study was to determine if fibrosis occurs during cachexia development, and to evaluate this in both sexes. Methods Female and male C57BL6/J mice were injected with PBS or Lewis Lung Carcinoma (LLC) at 8‐week of age and tumors were allowed to develop for 1, 2, 3, or 4 weeks. 3wk and 4wk female tumor‐bearing mice displayed a dichotomy in tumor growth and were reassigned to high tumor (HT) and low tumor (LT) groups. In vitro analyses were also performed on co-cultured C2C12 and 3T3 exposed to LLC conditioned media. Immunohistochemistry and quantitative PCR analysis were used to investigate fibrosis and fibrosis related signaling in skeletal muscle. Results Collagen deposition in skeletal muscle was increased in the 1wk, LT and HT groups in female mice. However, collagen deposition was only increased in the 4wk group in male mice. In general female mice displayed earlier alterations in ECM related genes beginning at 1 wk post-LLC injection. Whereas this was not seen in males. Conclusions While overall tumor burden is tightly correlated to cachexia development in both sexes, fibrotic development is not. Male mice did not exhibit early-stage alterations in ECM related genes contrary to what was noted in female mice.
22 Dec 2022Submitted to Cell Biochemistry & Function
01 Jan 2023Submission Checks Completed
01 Jan 2023Assigned to Editor
01 Jan 2023Review(s) Completed, Editorial Evaluation Pending
06 Jan 2023Reviewer(s) Assigned
14 Feb 2023Editorial Decision: Revise Major
16 Mar 20231st Revision Received
06 Apr 2023Submission Checks Completed
06 Apr 2023Assigned to Editor
06 Apr 2023Review(s) Completed, Editorial Evaluation Pending
06 Apr 2023Reviewer(s) Assigned
17 Apr 2023Editorial Decision: Accept