Tumor Microenvironment and Advances in Spheroid Tumor Studies | 3D Spheroids | Corning

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3D cell culture methods — and multicellular tumor spheroids (MCTs), in particular — are quickly becoming a valuable tool for studying the tumor microenvironment in cancer research.

Cancer scientists are creating increasingly complex tumor models that more accurately replicate in vivo conditions — including the tumor microenvironment, which plays a key role in tumor progression, according to a study published in BioTechniques.

MCTs mimic many of the features that tumors exhibit in the human body, including extracellular matrix (ECM) deposition between cells, gradients in nutrient concentration, and strong cell-cell junctions.

Products for Tumor Spheroid Growth and Development

The ECM a researcher chooses has a significant effect on cancer cell proliferation, initiation, invasion, and metastasis, and it alters how the tumor model responds to drug therapy. Hydrogel-based ECMs offer a variety of properties that allow researchers to scaffold MCTs and improve their similarity to in vivo tumors. According to a study published in Science Advances, Corning® Matrigel® matrix is the gold standard scaffold for MCT growth. It's mostly made up of laminin, type IV collagen, and entactin, and it also features growth factors and other constituents, such as proteoglycans.

3D collagen hydrogels are another commonly used ECM. No surprise there: Collagen is the most abundant fibrous protein found in mammals' ECMs, and it plays a critical role in tumor growth and metastasis because it promotes cell adhesion and migration. Collagen type I hydrogels have been used to grow MCTs from osteosarcomas, breast cancer cells, human colorectal cancer cells, prostate cancer cell lines, and primary cancer cells from colorectal cancer patients, according to the Science Advances study.

Recent Advances in Spheroid Tumor Studies

Producing tumor models that are comparable in size to tumors found in the body, though, has proven challenging. In August 2019, a team at Purdue University used scaffolds to create so-called macrotumors between 0.5 and 1 centimeters wide and 1.5 centimeters tall — much bigger than most tumor models, which are usually between 200 and 800 micrometers. These macrotumors remained viable for days — sometimes weeks — allowing the researchers to test therapeutic drugs.

Personalized cancer therapy is emerging as a critical strategy for treating tumors. Spheroids are an important part of this strategy, as they can be grown from cells harvested from tumor biopsies. A study published in Anticancer Research on head and neck cancers charted the development of a method for generating MCTs from tumor biopsies, the first step toward creating a method of assessing individual susceptibility to chemotherapy drugs and radiation therapy. The study's results confirmed previous findings that a treatment protocol of cisplatin and radiation was superior to radiation alone and confirmed the feasibility of using primary tumor cells for spheroid formation, which could yield MCTs that more closely mimic in vivo tumor behavior.

Spheroids in Metastatic Treatment

Metastatic treatment remains a challenge in oncology. MCTs can mimic metastatic microtumors, which form when cancer cells spread from the site of the primary tumor via intravasation into the blood circulation and via extravasation into the parenchyma of an organ. Thus MCT models are particularly useful, according to Science Advances, for developing therapies that target metastatic cells.

Spheroids have also been used to study transcoelomic metastasis in ovarian cancer, in which primary tumor cells seep into the abdominal cavity, where they form spheroids and then travel through fluids to secondary sites. Understanding fluid shear stress is critical in studying transcoelomic metastasis; modeling it in the tumor microenvironment, though, has been challenging. But a recent study in Cells used a dynamic culture method to produce spheroids under fluid shear stress in a lab environment. These spheroids will be used as a drug screening platform with enhanced in vivo characteristics that better mimic how cancer forms and spreads in the human body.