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Mechanobiology of Disease
Poster Abstracts
55
34-POS
Board 34
Relative Adhesion Profiler System for Biophysical Interrogation of Malignant Breast
Cancer Phenotypes
Harsha M. Kittur
1
, Andy Tay
1
, Avery Hua
1
, Min Yu
2
, Dino Di Carlo
1,3,4
.
1
UCLA, Los Angeles, CA, USA,
2
University of Southern California, Los Angeles, CA,
USA,
3
California NanoSystems Institute, Los Angeles, CA, USA,
4
Jonsson Comprehensive
Cancer Center, Los Angeles, CA, USA.
Breast cancer mortality is linked to metastasis and currently we lack sufficient biomarkers that
accurately predict locations of metastases, enabling improved treatment. We aim to complement
current genetic biomarkers with physiologically-relevant physical biomarkers associated with
cell adhesion and migration. Here, cells are seeded on a PDMS surface patterned with large
stripes of eight different extracellular matrix proteins, and are sandwiched from above with
another protein-coated surface with the same eight stripes running orthogonally, to interrogate
large groups of cells with 64 protein pair combinations. We quantified percent cell transfer to the
top surface for each protein pair over five breast cell lines with unique metastatic potential –
normal breast cells (hMEC), malignant breast cancer cells (MDA-MB-231) and MDA-MB-231
cells that have tropism to brain, lung, and bone – to generate relative adhesion plots that can
distinguish the populations. These heat maps generally reveal transfer of malignant cells toward
collagen 1, but also shows transfer away from basement membrane proteins collagen 4 and
laminin, regardless of the type of new protein that is introduced. Morphological analyses show
that hMEC display epithelial behavior favoring cell-cell contact via amoeboid motions as
opposed to adhesion to the new surface. In contrast, MDA-lung cells tend to move with a
mesenchymal phenotype as they switch to a new collagen 1 surface. Antibodies to alpha 2 and
beta 1, but not with alpha 6 integrins interfere with transfer. The actin cytoskeleton, but not
microtubules or myosin II are implicated in the transfer process. Finally, further analyses of
select protein pair combinations provide potential to develop protocols that can separate
malignant cells from non-cancerous cells, and then further delineate the malignant cells by their
tropism to specific secondary sites.