Mortalin antibody-conjugated quantum dot transfer from human mesenchymal stromal cells to breast cancer cells requires cell-cell interaction.
The role of tumor stroma in regulation of breast cancer growth has been widely studied. However, the details on the type of heterocellular cross-talk between stromal and breast cancer cells (BCCs) are still poorly known. In the present study, in order to investigate the intercellular communication between human mesenchymal stromal cells (hMSCs) and breast cancer cells (BCCs, MDA-MB-231), we recruited cell-internalizing quantum dots (i-QD) generated by conjugation of cell-internalizing anti-mortalin antibody and quantum dots (QD). Co-culture of illuminated and color-coded hMSCs (QD655) and BCCs (QD585) revealed the intercellular transfer of QD655 signal from hMSCs to BCCs. The amount of QD double positive BCCs increased gradually within 48h of co-culture. We found prominent intercellular transfer of QD655 in hanging drop co-culture system and it was non-existent when hMSCs and BBCs cells were co-cultured in trans-well system lacking imminent cell-cell contact. Fluorescent and electron microscope analyses also supported that the direct cell-to-cell interactions may be required for the intercellular transfer of QD655 from hMSCs to BCCs. To the best of our knowledge, the study provides a first demonstration of transcellular crosstalk between stromal cells and BCCs that involve direct contact and may also include a transfer of mortalin, an anti-apoptotic and growth-promoting factor enriched in cancer cells.
National Institute of Advanced industrial Sciences and Technology, Tsukuba, Ibaraki 305 8562, Japan.
Mika
M
Pietilä
Petri
P
Lehenkari
Paula
P
Kuvaja
Mika
M
Kaakinen
Sunil C
SC
Kaul
Renu
R
Wadhwa
Toshimasa
T
Uemura
D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003600:Cytosol / Q000378:metabolism; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D045663:Quantum Dots; D013194:Staining and Labeling
D000911:Antibodies, Monoclonal; D018840:HSP70 Heat-Shock Proteins; C080352:mortalin
Anti-mortalin antibody; Breast cancer cells; Co-culture; Human mesenchymal stromal cells; i-QDs