# The Role of Oncostatin M in the PDAC tumor microenvironment and macroenvironment

> **NIH NIH F31** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $30,306

## Abstract

Project Summary/Abstract
Pancreatic adenocarcinoma (PDAC) carries a 90% 5-year mortality due to the treatment refractory, highly
metastatic nature of the tumor and frequent, severe cachexia or unintentional weight loss induced by tumor.
Tumor cells interact with host cells locally to specify a highly desmoplastic microenvironment, but also induce
systemic changes in the macroenvironment, including wasting of fat and muscle. Inflammatory cytokines, such
as members of the Interleukin-6/GP130 family including IL-6 and LIF, contribute to both the microenvironment
and macroenvironment in PDAC. IL-6 and LIF promote tumor inflammation and progression, and both have been
implicated in cachexia. However, less is known about the other IL-6 family of cytokines, including Oncostatin M
(OSM). Preliminary studies support a central role for OSM in PDAC. OSM and its receptor, OSMR, are expressed
in human and murine tumors. High tumor expression of OSMR correlates with poor survival for PDAC patients.
OSM was elevated in plasma of mice with PDAC tumors. In vitro, OSM increased expression of OSMR in human
and murine tumor cells and stromal cells demonstrating feed-forward regulation. OSM induced compaction of
tumor spheroids in tumor cell/fibroblast co-cultures. In contrast, deletion of OSM but not OSMR, from hosts
decreased collagen deposition in the tumor microenvironment. While skeletal muscle wasting, was unaffected,
deletion of OSM/OSMR from the host accelerated cardiac wasting and cardiac dysfunction and reduced overall
activity in mice with PDAC tumors. These data demonstrate that OSM/OSMR signaling modulates both the tumor
microenvironment and macroenvironment in PDAC. Here we will test the following hypotheses in two Aims: 1)
OSM signaling on tumor cells through fibroblasts promotes the desmoplastic phenotype in PDAC. 2) OSM
signaling in the heart is protective of cardiac mass and function in PDAC cachexia. For AIM 1, Osm signaling
will be manipulated in monoculture and co-cultures studies using human and murine tumor and fibroblast cells;
mice deleted for OSM or OSMR will be orthotopically implanted with pancreatic cancer cells; tumor cells deleted
for OSMR will be implanted in wildtype mice; all will be evaluated by cell and molecular analysis. For AIM 2,
OSM and OSMR knockout mice will be implanted with PDAC tumor cells and evaluated for body weight change,
body composition, strength/function, cardiac function, and organ wasting. Muscle and heart will be harvested for
histomorphometry and molecular analysis. The training plan will provide the applicant with skills in CRISPR,
single cell sequencing, interpretation of omics data, immunophenotyping of tissues, cancer modeling, cardiac
dysfunction and oral and written communication. Training will take place at Indiana University School of
Medicine, a highly collaborative and resourced institution, under the direct advisement of Dr. Teresa Zimmers, a
well-published cancer cachexia researcher. Summarily, the...

## Key facts

- **NIH application ID:** 10314342
- **Project number:** 1F31CA265168-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Daenique Jengelley
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,306
- **Award type:** 1
- **Project period:** 2021-08-03 → 2023-08-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314342

## Citation

> US National Institutes of Health, RePORTER application 10314342, The Role of Oncostatin M in the PDAC tumor microenvironment and macroenvironment (1F31CA265168-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10314342. Licensed CC0.

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