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Topic: Brain tumor cell invasion and metastasis: anatomical, biological and clinical considerations

Brain infiltration by cancer cells: different roads to the same target?

Mayra Paolillo, Sergio Schinelli
Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy.
Correspondence to: Dr. Mayra Paolillo, Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy. E-mail: mayra.paolillo@unipv.it

Mayra Paolillo is research associate at the Drug Sciences Department, University of Pavia, Italy. Her researches
mainly deal with the study of functional effects and signal transduction pathways modulated by the pharmacological
blocking of RGD-binding integrins in glioma cancer stem cells and glioma cell lines.

A B S T R AC T
Brain infiltration by cancer cells is a complex process in which metastatic cells detached from the primary tumor must firstly
survive in the blood flow, cross the blood brain barrier (BBB) and finally colonize a foreign microenvironment. The cells that
successfully bypass the cellular barriers surrounding capillaries, proliferate to form micrometastasis and trigger the angiogenetic
process. Different molecular mechanisms have been proposed to explain the metastatic behaviour of solid tumors that infiltrate
brain tissue; in this review the most recent findings concerning mechanisms and genes potentially involved in brain metastasis,
that differ according to primary tumor types, will be discussed. The three tumors that more frequently develop brain metastasis,
lung cancer, breast cancer and melanoma, will be considered and, in addition, the role of BBB and the process of endothelial to
mesenchymal transition in cancer metastasis will be briefly described.

Key words: Brain metastasis; breast; epithelial-mesenchymal transition; lung; melanoma; micro-RNA

INTRODUCTION tumors that most often spread to the brain are lung cancer
(30-50% of patients) and breast cancer (10-30% of patients),
The prognosis for cancer patients is strictly dependent on with melanoma ranking at the 3rd place (6-10% of patients).
[3]
the metastatic behaviour of the tumor. Each tumor displays In many cases, the poor life expectancy associated with BM
preferential sites were metastases more frequently develop is due to other widespread metastasis but this is not true for
and patients survival depends upon the possibility to perform melanoma patiens, who very early display BM that make
surgery followed by oncological therapy and radiotherapy. unsuccessful further therapeutic efforts. [4]
Indeed, these approaches are usually sufficient to eradicate
local oligometastases but unfortunately the picture is Without treatment, median survival for a patient with BM is
different in the case of brain metastases (BM), which are estimated to be about 3 months for a single lesion, although life
frequently associated with a poor prognosis. In the case expectancy has recently increased due to enhanced diagnostic
[1]
of BM, stereotaxic radiosurgery is a useful tool to reduce tools that may even detect very tiny neoplastic formations. [4]
local recurrence and achieve the same level of local control
of whole-brain radiation therapy, with fewer side effects and Cancer cells traveling through the bloodstream eventually
comparable outcomes. [2] colonize a vascular place, by adhering to endothelial cells, or

BM affect up to 40% of metastatic cancer patients and the This is an open access article distributed under the terms of the Creative
[1]
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
Access this article online the author is credited and the new creations are licensed under the identical
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Website: For reprints contact: service@oaepublish.com
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How to cite this article: Paolillo M, Schinelli S. Brain infiltration by
cancer cells: different roads to the same target? J Cancer Metastasis
DOI: Treat 2016;2:90-100.
10.4103/2394-4722.172661
Received: 10-10-2015; Accepted: 30-11-2015.

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