Childhood Cancer Data Initiative Annual Symposium (Abstract Registration): Submission #66

Submission information
Submission Number: 66
Submission ID: 190730
Submission UUID: 6d298f83-d0e0-4a1d-a528-b525c43c8309

Created: Wed, 08/12/2026 - 13:00
Completed: Wed, 08/12/2026 - 13:07
Changed: Wed, 08/12/2026 - 13:07

Remote IP address: 10.208.28.62
Submitted by: Anonymous
Language: English

Is draft: No
Abstract Title: Repurposing Anti-Fibrotic Strategies to Target Type II Pneumocyte-Driven Osteosarcoma Metastatic Progression
Abstract: Pulmonary metastasis is the leading cause of mortality in human and canine osteosarcoma (OS) patients, yet the contribution of lung-resident type II pneumocytes (TIIPs) to metastatic progression is under-defined. This study characterizes the distribution of pneumocytes in the OS lung metastasis microenvironment, defines the consequences of TIIP-OS crosstalk, and identifies a therapeutic strategy to limit pulmonary metastatic progression. Spatial transcriptomics and complementary IHC staining of human, canine, and murine OS lung metastases showed increased TIIP accumulation at the tumor:non-tumor interface compared to distal lung parenchyma. Indirect co-culture of human primary TIIPs with MG63.2 OS cells significantly increased tumor cell proliferation, an effect reproduced with TIIP-conditioned media, suggesting that soluble TIIP-derived factors are pro-tumorigenic. RNA sequencing of co-cultured TIIPs showed enrichment of the p53 pathway, consistent with an injury/stress response resembling idiopathic pulmonary fibrosis. Cytokine profiling and Enrichr pathway analysis identified a pro-fibrotic secretome as a dominant feature of TIIP-OS crosstalk. Targeting TGF-β-mediated fibrosis with a dual integrin inhibitor reduced K7M2 OS proliferation in TIIP co-culture but not in monoculture, suggesting that the anti-proliferative effect is mediated through disruption of TIIP-OS crosstalk. A K7M2-pEGFP experimental metastasis model treated with 5 mg/kg or 25 mg/kg inhibitor showed significant dose-dependent reductions in metastases versus vehicle control. These findings provide the first cross-species characterization of TIIP spatial distribution within the OS pulmonary metastatic niche, demonstrating that TIIPs establish a growth-permissive, pro-fibrotic crosstalk with tumor cells. Disrupting this crosstalk represents a promising therapeutic strategy to limit metastatic progression and improve survival outcomes for OS patients.
Authors:
  1. First Name: Janice
    Middle Initial: S
    Last Name: Pereira
    Degree(s): Ph.D
    Organization: NCI, NIH
  2. First Name: Lauren
    Middle Initial: E
    Last Name: McGee
    Degree(s): Ph.D
    Organization: NCI, NIH
  3. First Name: Anjali
    Last Name: Garg
    Degree(s): Ph.D
    Organization: NCI, NIH
  4. First Name: Kate
    Middle Initial: I
    Last Name: Silver
    Degree(s): BS
    Organization: NCI, NIH
  5. First Name: Troy
    Middle Initial: A
    Last Name: McEachron
    Degree(s): Ph.D
    Organization: NCI, NIH
  6. First Name: Christina
    Last Name: Mazcko
    Degree(s): BS
    Organization: NCI, NIH
  7. First Name: Jessica
    Middle Initial: A
    Last Name: Beck
    Degree(s): DVM Ph.D DACVP
    Organization: NCI, NIH and OSU
  8. First Name: Amy
    Middle Initial: K
    Last Name: LeBlanc
    Degree(s): DVM
    Organization: NCi, NIH
Presenting Author: Janice S. Pereira
Institution: NCI, NIH
Email Address: janice.pereira@nih.gov