Next Article in Journal
Targeting Adenosine Receptor Signaling in Cancer Immunotherapy
Next Article in Special Issue
Annexin A1 May Induce Pancreatic Cancer Progression as a Key Player of Extracellular Vesicles Effects as Evidenced in the In Vitro MIA PaCa-2 Model System
Previous Article in Journal
CRISPR/Cas9-Mediated Deletion of Large Genomic Fragments in Soybean
Previous Article in Special Issue
Emerging Role of Immune Checkpoint Blockade in Pancreatic Cancer
Open AccessArticle

Local and Systemic Cytokine Profiling for Pancreatic Ductal Adenocarcinoma to Study Cancer Cachexia in an Era of Precision Medicine

1
Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA
2
Department of Physical Therapy, University of Florida Health Science Center, Gainesville, FL 32610, USA
3
Department of Neurosurgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA
4
North Florida/South Georgia Veterans Health System, Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA
5
Departments of Cancer Epidemiology and Gastroinestinal Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA
6
Department of Foundational Sciences, School of Dental Medicine, East Carolina University, Greenville, NC 27834, USA
*
Author to whom correspondence should be addressed.
These authors have contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(12), 3836; https://doi.org/10.3390/ijms19123836
Received: 21 October 2018 / Revised: 20 November 2018 / Accepted: 28 November 2018 / Published: 1 December 2018
(This article belongs to the Special Issue Cell and Molecular Biology of Pancreatic Disorders)
Cancer cachexia is a debilitating condition seen frequently in patients with pancreatic ductal adenocarcinoma (PDAC). The underlying mechanisms driving cancer cachexia are not fully understood but are related, at least in part, to the immune response to the tumor both locally and systemically. We hypothesize that there are unique differences in cytokine levels in the tumor microenvironment and systemic circulation between PDAC tumors and that these varying profiles affect the degree of cancer cachexia observed. Patient demographics, operative factors, oncologic factors, and perioperative data were collected for the two patients in the patient derived xenograft (PDX) model. Human pancreatic cancer PDX were created by implanting fresh surgical pancreatic cancer tissues directly into immunodeficient mice. At PDX end point, mouse tumor, spleen and muscle tissues were collected and weighed, muscle atrophy related gene expression measured, and tumor and splenic soluble proteins were analyzed. PDX models were created from surgically resected patients who presented with different degrees of cachexia. Tumor free body weight and triceps surae weight differed significantly between the PDX models and control (P < 0.05). Both PDX groups had increased atrophy related gene expression in muscle compared to control (FoxO1, Socs3, STAT3, Acvr2b, Atrogin-1, MuRF1; P < 0.05). Significant differences were noted in splenic soluble protein concentrations in 14 of 15 detected proteins in tumor bearing mice when compared to controls. Eight splenic soluble proteins were significantly different between PDX groups (P < 0.05). Tumor soluble proteins were significantly different between the two PDX groups in 15 of 24 detected proteins (P < 0.05). PDX models preserve the cachectic heterogeneity found in patients and are associated with unique cytokine profiles in both the spleen and tumor between different PDX. These data support the use of PDX as a strategy to study soluble cachexia protein markers and also further efforts to elucidate which cytokines are most related to cachexia in order to provide potential targets for immunotherapy. View Full-Text
Keywords: pancreatic cancer; cachexia; cytokines; innate immune system pancreatic cancer; cachexia; cytokines; innate immune system
Show Figures

Graphical abstract

MDPI and ACS Style

Gerber, M.H.; Underwood, P.W.; Judge, S.M.; Delitto, D.; Delitto, A.E.; Nosacka, R.L.; DiVita, B.B.; Thomas, R.M.; Permuth, J.B.; Hughes, S.J.; Wallet, S.M.; Judge, A.R.; Trevino, J.G. Local and Systemic Cytokine Profiling for Pancreatic Ductal Adenocarcinoma to Study Cancer Cachexia in an Era of Precision Medicine. Int. J. Mol. Sci. 2018, 19, 3836.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop