The Role of Laminins on Cancer Cell Migration and Invasion

Abstract

Breast cancer is one of the deadliest cancers and the most common cancer in women. In 2018 over 2 million cases were diagnosed, which makes breast cancer the second most common cancer after lung cancer. About every third diagnosed died in 2018 and that makes breast cancer a leading cause of cancer deaths in over 100 countries. Main cause of death in breast cancer is when the cancer cells metastasize and form metastatic tumors.

The aim of this project was to study the effects of different laminins on MDA-MB 231 breast cancer cell migration and invasiveness. The chosen laminins were laminin -111, -421 and -521. There were two different kinds of experiments: cell culture inserts that studied the invasiveness, and Cell-IQ that was used to study the migration on 2D surface. The experiments were also done with siRNA treated cells downregulating either integrin β-1 or integrin β-4, which both adhere to laminins.

The project started with defining the suitable quantity of cells for inserts, which was settled in couple of weeks to 100 000 cells. Different laminins started showing significant differences on their invasiveness and highest speed of invasion was on laminin 111. Least invasive the cells were on laminin 521. The Cell-IQ started showing clear differences between laminins on motility on 2D surface. Highest movements could be recorded on laminin 421 and 521 and slowest on laminin 111. The cell started to express different kinds of morphologies depending on laminin. On laminin 111 the cell curled up to small balls and on laminin 521 the cells spread out notably, which could have had an impact on the invasiveness through the insert membrane. The downregulation of integrins β-1 and β-4 was not as effective as hoped, except on the first experiment. Interestingly, the first week’s experiments on laminin 111 with downregulated β-1 integrin, gave over four times higher result than the Fluc treated, which worked as a control. On Cell-IQ experiments, it was noticed that the downregulation of integrin β-1 seemed to decrease the motility of the cells. On laminin 521, downregulation of integrin β-4 had slightly increasing effects on cell motility.