Abstract
Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.
Highlights
Metastases cause more than 90% of cancer patient death [1]
Former studies concentrate on enzymes as lysyl oxidase (LOX) or proteases like the MMPs responsible for remodeling extracellular matrix (ECM), here we focus on studies about targeting key ECM proteins
Targeting of ECM components holds much promise for improved cancer management, it is important to keep in mind that any treatment aimed at cancer ECM may affect the same ECM component in healthy tissue
Summary
Metastases cause more than 90% of cancer patient death [1]. The spread of the tumor cells to secondary sites of the body is a complex process involving reciprocal interaction between tumor cells and their microenvironment [2]. LMW-HA is angiogenic [62], so the production of LMW-HA fragments in the tumor microenvironment can compromise the tumor vessel integrity and promote angiogenesis, making it easier for cancer cells to intravasate and continue the metastatic process Studies of both patient material and mouse models of cancer have shown that the deposition of a collagen-rich matrix is linked to tumor progression and metastasis [47]. Tavazoi et al were able to diminish the invasive potential of a metastatic breast cancer cell line by knocking down tenascin C expression These cells were deprived of the ability to form lung metastasis in vivo [82]. Oskarsson et al could even demonstrate a deposition of tenascin C at the margin of lung metastases of both mice injected with the breast cancer cell line MDA231-LM2 and breast cancer patient samples [23]
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