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Callaway CS, Delitto AE, Patel R, et al. IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy. Cancers (Basel). 2019;11(12)doi: 10.3390/cancers11121863.
Callaway, C. S., Delitto, A. E., Patel, R., Nosacka, R. L., D'Lugos, A. C., Delitto, D., Deyhle, M. R., Trevino, J. G., Judge, S. M., & Judge, A. R. (2019). IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy. Cancers, 11(12), . https://doi.org/10.3390/cancers11121863
Callaway, Chandler S, et al. "IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy." Cancers vol. 11,12 (2019). doi: https://doi.org/10.3390/cancers11121863
Callaway CS, Delitto AE, Patel R, Nosacka RL, D'Lugos AC, Delitto D, Deyhle MR, Trevino JG, Judge SM, Judge AR. IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy. Cancers (Basel). 2019 Nov 25;11(12). doi: 10.3390/cancers11121863. PMID: 31769424; PMCID: PMC6966692.
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Cancers (Basel). 2019 Nov 25;11(12). doi: 10.3390/cancers11121863.

IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy.

Cancers

Chandler S Callaway, Andrea E Delitto, Rohan Patel, Rachel L Nosacka, Andrew C D'Lugos, Daniel Delitto, Michael R Deyhle, Jose G Trevino, Sarah M Judge, Andrew R Judge

Affiliations

  1. Department of Physical Therapy, University of Florida, Gainesville, FL 32610, USA.
  2. Department of Surgery, University of Florida, Gainesville, FL 32610, USA.

PMID: 31769424 PMCID: PMC6966692 DOI: 10.3390/cancers11121863

Abstract

Tumor-derived cytokines are known to drive the catabolism of host tissues, including skeletal muscle. However, our understanding of the specific cytokines that initiate this process remains incomplete. In the current study, we conducted multiplex analyte profiling of cytokines in conditioned medium (CM) collected from human pancreatic cancer (PC) cells, human tumor-associated stromal (TAS) cells, and their co-culture. Of the factors identified, interleukin-8 (IL-8) is released at high levels from PC cells and PC/TAS co-culture and has previously been associated with low muscle mass in cancer patients. We, therefore, treated C2C12 myotubes with IL-8 which led to the activation of ERK1/2, STAT, and Smad signaling, and induced myotube atrophy. Moreover, the treatment of mice with IL-8 also induced significant muscle wasting, confirming the in vivo relevance of IL-8 on muscle. Mechanistically, IL-8-induced myotube atrophy is inhibited by treatment with the CXCR2 antagonist, SB225002, or by treatment with the ERK1/2 inhibitor, U0126. We further demonstrate that this axis mediates muscle atrophy induced by pancreatic cancer cell CM, as neutralization of IL-8 or treatment with SB225002 or U0126 significantly inhibit CM-induced myotube atrophy. Thus, these data support a key role of IL-8 released from human PC cells in initiating atrophy of muscle cells via CXCR2-ERK1/2.​.

Keywords: cachexia; interleukin-8; muscle wasting

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the dec

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