Stimulation of extracellular matrix components in the normal brain by invading glioma cells

Abstract

Malignant gliomas are characterized by an extensive invasion of tumor cells into the normal brain parenchyma. A substantial amount of data indicates that cell movement in general is regulated by specific interactions between extracellular matrix components and specific cell-surface receptors. In the present work, multicellular spheroids from 4 human glioma cell lines (U-373Mg, A-172Mg, U-251Mg and HF-66) were confronted with normal rat brain cell aggregates in vitro, which resulted in a progressive invasion of tumor cells into the brain aggregates. The co-cultures were then sectioned and immuno-stained for specific extracellular matrix components (laminin, fibronectin and collagen type IV) and for specific cell-surface receptors which bind to these components (integrins ␤ 1 , ␤ 4 , ␣ 3 , ␣ 6 ). In addition, flow-cytometric measurements and Northern blot analyses showed expression of several different integrins within the cell lines. The ␣ 3 subunit was expressed strongly in all cell lines. Whereas the ␤ 1 subunit was expressed weakly in exponentially growing monolayer cultures, it showed a pronounced expression in multicellular spheroids, indicating that the integrin expression may vary depending on the micro-environment within a tumor. Furthermore, normal brain tissue was able to produce laminin when confronted with the glioma cells, which also was observed for fibronectin and collagen type IV. The relevance of our observations to the in vivo situation was investigated further by immuno-staining 5 human glioma biopsy samples for laminin. In some areas of the tumors, specific deposits of laminin were observed. In conclusion, we have shown that normal brain tissue has the ability to produce extracellular matrix components, such as laminin, collagen type IV and fibronectin, when confronted with invading glioma cells. Our results show that the glioma cells express specific integrins which can interact with these extracellular matrix components. Such interactions may facilitate tumor cell migration and invasion. Int.

Glioma infiltration and extracellular matrix: key players and modulators

“…Particularly, aberrant expression of the b1 subunit can promote glioma infiltration (Friedlander et al, 1996;Paulus, Baur, Beutler, & Reeves, 1996). a3b1 has been shown to be consistently overexpressed and to be a key regulator of glioma cell migration (Fukushima, Ohnishi, Arita, Hayakawa, & Sekiguchi, 1998;Knott et al, 1998;Zhou et al, 2015). In addition, avb3 (observed at the periphery of high-grade gliomas) and avb5 integrins (expressed more at the center of the tumor) are involved in glioma malignancy (Bello et al, 2001;Gladson, 1996;Mittelbronn, Warth, Meyermann, Goodman, & Weller, 2013;Rooprai et al, 1999).…”

Modulation of hyaluronan production by CD44 positive glioma cells

“…2,[5][6][7] During this process, certain chondroitin sulfate (CS) proteoglycans (PGs) and HA are synthesized and released into the microenvironment. [8][9][10] Some ECM components and CD44 are found at the invasion front of several tumors, including glioma, at the interface with normal tissue, e.g., with brain tissue. [11][12][13][14][15][16] The ECM environment of the brain, rich in HA, [17][18][19][20][21] provides hydrated spaces that facilitate glioma cell migration and angiogenesis.…”

Increased expression of integrin α3β1 in highly brain metastatic subclone of a human non‐small cell lung cancer cell line

“…5) However, it is known that ECM and integrin play important roles in the progression of brain tumors. 6) Progression of glioma in the brain is correlated with the laminin distribution. Glioma cells recognize laminin through the cell surface integrin α3β1.…”