6 Stiffening of tissue has been correlated with a poor prognosis and softening of tissue reduces metastasis and disease progression in mouse models of breast carcinoma. 3 These changes in tissue reorganization have broad-reaching effects on cancer cells. Here we know that the tumor microenvironment becomes mechanically stiff due to accumulation and reorganization of extracellular matrix proteins and activation of stromal fibroblasts.
INTERSTITIAL FLUID SKIN
The biophysical microenvironment of the tumor has been best studied in breast cancer, the second most frequently occurring cancer next to skin cancer. 1 Biophysical forces such as stromal stiffening, 3 interstitial pressure, 4 and fluid flow 5 have a number of effects on the ability of therapy to both reach the tumor microenvironment and induce the desired response in cancer cells. 1, 2 Biologically, cancer-associated cells, such as fibroblasts and immune cells, can affect therapeutic resistance in ways that are still being elucidated. Biochemically, cancer and cancer-associated cells secrete a number of cytokines to sustain their growth and development that can interfere with the success of antiproliferative therapeutics, including antimitotics, DNA intercalating agents, and receptor tyrosine kinase inhibitors. These include biophysical and biochemical barriers. That being said, there are parallels amongst the different solid tumors and their associated microenvironments that may impede the efficacy of cancer therapies. These components, including cells and extracellular matrix proteins, and growth factors, can vary based on the tissue stroma in which the cancer forms. This tumor microenvironment includes all of the cells and tissue components aside from the cancer. Keywords: tumor microenvironment, interstitial flow, therapeutics, invasionĪlthough cancer arises from transformation of single cells, once a tumor initiates, the surrounding tissue is altered to promote cancer survival and growth. By stating the current understanding of interstitial flow in cancer progression, we can begin exploring its role in therapeutic failure and treatment resistance. We also discuss the current role of fluid flow in the treatment of cancer, including drug transport and therapeutic strategies. Here we outline the current understanding of the role of interstitial flow in cancer and the tumor microenvironment through cancer progression and therapy. This invasion is one mechanism by which cancers can resist therapeutics and recur, but the role of interstitial flow in cancer therapy is limited to the understanding of transport of therapeutics. With research spanning the past decade, we have seen that interstitial flow has a promigratory effect on cancer cell invasion in multiple cancer types. Until recently, the role of interstitial flow was thought to be mostly passive in the transport and dissemination of cancer cells to metastatic sites. Increased intratumoral pressure and corresponding increases in interstitial flow from the tumor bulk to the healthy stroma is an observational hallmark of progressing cancers. Given the good sampling and in situ monitoring ability, the MN array holds great promise for skin ISF-based applications.1Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 2School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USAĪbstract: As cancer progresses, a dynamic microenvironment develops that creates and responds to cellular and biophysical cues. For proof-of-concept, it realizes detection of miRNAs and Cu 2+ efficiently and quantitatively in an agarose skin and fresh porcine cadaver skin model.
INTERSTITIAL FLUID PATCH
The MN patch displays good mechanical properties that enable withstanding more than 0.4 N per needle, and exhibits a high swelling ratio of 700% that facilitates timely extraction of sufficient ISF for biomarker analysis. The MN array is made of methacrylated gelatin (GelMA) and methacrylated hyaluronic acid (MeHA), and a further divisionally encapsulated miRNA and Cu 2+ detection system, and is cross-linked through blue-light irradiation. The present work describes an attractive MN sensor array for minimally invasive monitoring of ISF microRNA (miRNA) and Cu 2+. Microneedle (MN) integration of sampling and instant biomarker readout hold great potential in health status monitoring and point-of-care testing (POCT).
Skin interstitial fluid (ISF) is a biofluid with information-rich biomarkers for disease diagnosis and prognosis.
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