NCI Division of Cancer Biology Junior Investigators Meeting (Abstract): Submission #2

serial: '2'
sid: '190397'
uuid: 592a2cf6-cf03-4d47-a870-fb3684ff3479
uri: /dcb/ji-meeting/abstract
created: '1786385237'
completed: '1786385237'
changed: '1786385237'
in_draft: '0'
current_page: ''
remote_addr: 10.208.28.62
uid: '0'
langcode: en
webform_id: nci_junior_investigator_abstract
entity_type: node
entity_id: '1818'
locked: '0'
sticky: '0'
notes: ''
metatag: meta
data:
  category: 'Consider my abstract for a Methodology/Technology presentation'
  degree_s_: B.S
  email: squijano@purdue.edu
  first_name: Sydney
  keywords_abstracts: ''
  last_name: Quijano
  middle_initial: ''
  organization: 'Purdue University'
  organization_address:
    address: ''
    address_2: ''
    city: 'West Lafayette Indiana'
    country: ''
    postal_code: ''
    state_province: ''
  summary: |
    Following establishment and treatment of primary disease, systemically disseminated breast cancer cells can remain dormant for years only to evolve into therapy-resistant metastases. Specific environmental influences that contribute to the transition from dormant to metastatic disease remain poorly characterized. Herein, we utilized mouse models to evaluate the influence of alcohol consumption on emergence from pulmonary dormancy. Consistent with prior reports, we found that animals consuming alcohol demonstrated decreased adaptive immune presence and increased extracellular matrix deposition in their lungs compared to non-drinking counterparts. Seeding the D2.OR model of pulmonary dormancy cells followed by alcohol consumption caused outgrowth of macroscopic lesions. Isolation and culture of these tumors produced an independent subline (D2.OR-EtOH) capable of pulmonary outgrowth upon reinjection into immunocompetent, alcohol naïve animals. Gene expression analysis of D2.OR-EtOH indicated downregulation of the serine peptidase inhibitor Kazal type 5 (SPINK5) compared to parental cells. Genetic depletion of SPINK5 from parental D2.OR cells was sufficient to allow pulmonary outgrowth in vivo. Evaluation of the immune infiltrate into alcohol-induced pulmonary lesions demonstrated high numbers of neutrophils and the formation of neutrophil extracellular traps (NETs), structures associated with breakage of pulmonary dormancy. D2.OR-EtOH subline and SPINK5-depleted D2.OR cells more readily induced NET formation when cocultured with neutrophils. Overall, our studies demonstrate that alcohol consumption can break pulmonary dormancy by altering the interaction of tumor cells with innate immune cells. Furthermore, our work identifies SPINK5 as an important contributor to metastatic progression in breast cancer through its regulation of interacting neutrophils. 
  title: 'Graduate Student '
  ttile: 'Loss of SPINK5 mediates the outgrowth of disseminated breast cancer '