title: Exosomes in Human Breast Milk Promote EMT.
abstract: OBJECTIVE
  Pregnancy increases breast cancer risk for all women for at least 5 years after parturition. During weaning and involution, the breast microenvironment becomes tumor promotional. Exosomes provide cell-cell communication during physiologic processes such as lactation, but also in breast cancer. We determined whether molecules in milk exosomes from healthy lactating women modulate the development and progression of breast cancer.
  
  
  METHODS
  Thirteen nursing women provided three (transitional, mature, and wean) milk samples. Exosomes were extracted and MCF7 and MCF10A breast cells labeled. The expression of six proteins linked to breast cancer was measured. On the basis of the findings, TGFβ2 concentration in exosome samples was measured, breast cells incubated with the exosomes and effect (epithelial-mesenchymal transition, EMT) on EMT-related proteins [E-cadherin, α-smooth muscle actin (α-SMA), filamentous (F)-actin and vimentin] measured.
  
  
  RESULTS
  Human milk exosomes entered benign and malignant breast cells. The greatest change in wean milk protein was in TGFβ2 (P = 0.01). Exosomes with a high (but not low) level of TGFβ2 led to EMT in both cancer and benign cells, based on (i) change in cell morphology, actin cytoskeleton, and loss of cell-cell junction structure and (ii) increased α-SMA and vimentin and decreased E-cadherin.
  
  
  CONCLUSIONS
  TGFβ2 is significantly upregulated in breast milk exosomes during weaning/early involution. Breast milk exosomes containing high levels of TGFβ2 induce changes in both benign and malignant breast epithelial cells, consistent with the development and progression of breast cancer, suggesting a role for high TGFβ2-expressing breast milk exosomes in influencing breast cancer risk. Clin Cancer Res; 22(17); 4517-24. ©2016 AACR.
authors.affiliation: Department of Cellular & Molecular Biology, University of Texas Health Science Center, Tyler, Texas. Department of Surgery, University of Texas Health Science Center, Tyler, Texas.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Cellular & Molecular Biology, University of Texas Health Science Center, Tyler, Texas.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tsukasaki
authors.affiliation: Department of Cellular & Molecular Biology, University of Texas Health Science Center, Tyler, Texas.
authors.forename: Santanu
authors.initials: S
authors.lastname: Dasgupta
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Nitai
authors.initials: N
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Cellular & Molecular Biology, University of Texas Health Science Center, Tyler, Texas.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ikebe
authors.affiliation: Department of Cellular & Molecular Biology, University of Texas Health Science Center, Tyler, Texas. Department of Surgery, University of Texas Health Science Center, Tyler, Texas. edward.sauter@uthct.edu.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Sauter
mesh_terms: D000328:Adult; D015415:Biomarkers; D001943:Breast Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007774:Lactation; D008894:Milk Proteins / Q000378:metabolism; D008895:Milk, Human / Q000378:metabolism*; D011247:Pregnancy; D053781:Transforming Growth Factor beta2 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008894:Milk Proteins; C509041:TGFB2 protein, human; D053781:Transforming Growth Factor beta2