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Tumor‐Associated Protrusion Fluctuations as a Signature of Cancer Invasiveness
Author(s) -
Caballero David,
Brancato Virginia,
Lima Ana C.,
Abreu Catarina M.,
Neves Nuno M.,
Correlo Vitor M.,
Oliveira Joaquim M.,
Reis Rui L.,
Kundu Subhas C.
Publication year - 2021
Publication title -
advanced biology
Language(s) - English
Resource type - Journals
ISSN - 2701-0198
DOI - 10.1002/adbi.202101019
Subject(s) - biology , cancer , beach morphodynamics , cancer cell , metastasis , tumor progression , sediment transport , paleontology , genetics , sediment
The generation of invasive fluctuating protrusions is a distinctive feature of tumor dissemination. During the invasion, individual cancer cells modulate the morphodynamics of protrusions to optimize their migration efficiency. However, it remains unclear how protrusion fluctuations govern the invasion of more complex multi‐cellular structures, such as tumors, and their correlation with the tumor metastatic potential. Herein, a reductionist approach based on 3D tumor cell micro‐spheroids with different invasion capabilities is used as a model to decipher the role of tumor‐associated fluctuating protrusions in cancer progression. To quantify fluctuations, a set of key biophysical parameters that precisely correlate with the invasive potential of tumors is defined. It is shown that different pharmacological drugs and cytokines are capable of modulating protrusion activity, significantly altering protrusion fluctuations, and tumor invasiveness. This correlation is used to define a novel quantitative invasion index encoding the key biophysical parameters of fluctuations and the relative levels of cell‐cell/matrix interactions, which is capable of assessing the tumor's metastatic capability solely based on its magnitude. Overall, this study provides new insights into how protrusion fluctuations regulate tumor cell invasion, suggesting that they may be employed as a novel early indicator, or biophysical signature, of the metastatic potential of tumors.