Rupleen Kaur

MD/PhD Student | Case Western Reserve University

Intro to Premetastatic Niches and Tumor Secreted Factors

August 04, 2022

During the last few weeks, my search for a project led me to develop an interest in the topic of Premetastatic Niches. I am by no means an expert and my goal with this blog is to share some of what I learn as a graduate student.

It has been known for a while that tumors have a propensity to metastasize to distinct organs in the body. In the year 1889, Stephen Paget came up with his “seed and soil hypothesis” according to which metastasis was dependent on the interaction between the seeds (circulating cancer cells) and the soil (whatever place in the body the cancer cells were trying to occupy). It was challenged in 1930s by James Ewing who believed that the location of the metastasis was determined by the dynamics of the blood/lymph flow. This was the prevailing hypothesis until the 1970s when Isaiah Fidler showed that successful colonization was site dependent. That is, certain properties of a specific premetastatic site (apart than its location) predisposed it to being colonized by a circulating cancer cell.

It brings up a few important questions - what was this predisposing factor? Was the identity of this ‘factor’ different for different tumors, predisposing certain sites for metastasis more than others?
These factors secreted by the tumor were somehow inducing the formation of a microenvironment in a distant site, making it more conducive for the tumors survival, even at an early tumor stage. These pre-metastatic predisposed sites were termed “premetastatic niches” (PMN), and the factors predisposing them, tumor-secreted factors.
A lot of research has been done to try and identify these tumor-secreted factors, the details of which are beyond the scope of this post. I have included below a table (from a review by Hector Peinado) that lists the different organ-specific factors. Some of these factors are present on the tumor cells while others are secreted (either freely or via exosomes). In my next post, I will be writing about the process/timeline of PMN formation.
Tumor-associated factors (Hector Peinado's 2017 review paper)


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