Biophysical Society Thematic Meeting

Mechanobiology of Disease

Poster Abstracts

1-POS

Board 1

Defining the Mechanical-Phenotype Niche in Cancer through the Lens of Physics

Hong Lam, Jennifer Pluznick, William Isaacs, Kenneth Pienta,

Steven An

Johns Hopkins University, Baltimore, MD, USA.

A defining hallmark of primary and metastatic cancers is the invasion of malignant cells through

surrounding tissues. In this metastatic-invasion framework, the abilities of an individual cancer

cell to evade its primitive tumor ecosystem, to emigrate through its local stroma constituting a

tortuous extracellular matrix (ECM), and to disseminate to a distant target organ entail, in time

and space, mechanical transgression in the cell-cell and cell-matrix interactions. However

explicit this mechanical interplay might appear, to date, the rudimentary physics of cancer cell

metastasis is not fully explained. It remains equally unclear what cancers are primed to sense and

avoid, how these external chemical and/or mechanical cues are assimilated, and to what extent

these signals are hardwired to mechanical forces driving local cellular motions to metastatic-

invasion of cancers. Here we applied a constellation of enabling engineering platforms to trace

the evolution of biophysical events that culminate in cancer metastasis at single-cell resolution.

Across the experimental cancer models, we found increased dispersion of metastatic cancer cells

on collagen matrix that was universally accompanied by faster cytoskeletal remodeling dynamics

and emergent distribution of traction stresses at the cell-matrix interface. In addition, the local

tractions were precisely tuned to the surrounding matrix rigidity with the concomitant expression

of mechanosensitive integrin receptors. Unexpectedly, in prostate cancer (PCa), we found

expression of classical odorant “sensory” receptors belonging to the superfamily of G protein-

coupled receptors (GPCRs) and identified a number of olfactory receptors (ORs) that were

differentially expressed in localized vs. metastasized PCa. Because ORs are broadly expressed

and reported to play diverse homeostatic roles–i.e. sperm chemotaxis and muscle cell migration–

we are now studying physiologic and/or pathologic roles for de novo identified PCa ORs and

olfactory-like chemosensory signaling in PCa metastasis.