Saturday, March 19, 2011

One Renegade Cell by Robert A. Weinberg

At any moment, the great majority of cells in our body are in a quiescent state. Only in tissues that renew themselves constantly, such as the colonic epithelium, the bone marrow (which generates new blood cells), and the skin, does one find large numbers of cells actively growing and dividing. How precisely do any cells know when they should or should not grow?

Although each cell carries an extraordinarily elaborate data bank in its genes, these genes cannot provide the cell with some very critical pieces of information. Genes cannot tell a cell where it is in the body, how it arrived there, or whether the body requires it to grow. Genes can only tell the cell how it should respond to external signals, which must come from elsewhere – from other cells, nearby and distant in the body. Each cell in the body relies on a host of other cells to tell it where it is, how it got there, and what it should be doing. Among other information provided by its neighbors ( nearby and distant) are instructions that tell a cell when it should grow.

Complex organisms could not be organized otherwise. Cells exist in condominiums with other cells, forming tissues, organs, and ultimately whole organisms. The behavior of an individual cell in these communities must be dictated by the needs of the organism around it. Hence, each cell must be in close and constant contact with many other cells in the organism; these contacts form the network that binds this community together. While cells within a tissue are physically tethered to one another, they are tied even more importantly by incessant chatter.

A normal tissue is thus a network of millions of cells in constant communication, passing information to one another about their respective needs. How does a malignant tissue fit into this pattern? What characterizes the behavior of a cancer cell that arises in the midst of a crowd of normal neighbors?

The cancer cell is a renegade. Unlike their normal counterparts, cancer cells disregard the needs of the community of cells around them. Cancer cells are only interested in their own proliferative advantage. They are selfish and very unsociable. Most important, unlike normal cells, they have learned to grow without any prompting from the community of cells around them.

Cancer begins with a single renegade cell which succeeds in subverting normal regulatory processes of cell growth . The creation of a tumor is extraordinarily slow , often extending over decades. The cells forming a tumor are all lineal descendants of a single progenitor, a distant ancestor that lived many years before the tumor mass became apparent. This founder, this renegade cell, decided to go off on its own, to begin its own growth program within one of the body’s tissues. Thereafter, its proliferation was controlled by its own internal agenda rather than the needs of the community of cells around it.

So there were no millions of recruits, only a single one that spawned a vast horde of like minded descendants. The billions of cells in a tumor are cast in the image of their renegade ancestor. They have no interest in the well-being of the tissue and organism around them. They have only one program in mind: more growth, more replicas of themselves, unlimited expansion.

The chaos they create makes it clear how very dangerous it is to entrust each cell in the human body with its own measure of independence. Still, that is how we are put together, and how all complex, many-celled organisms have been designed for the past 600 million years. Learning this, we realize that the chaos of cancer is not a modern affliction but a risk run by all multicellular organisms, from ancient to modern. Indeed, given the trillions of cells in the human body-their hugely complex and unceasing activity providing, until recently, an almost unknowable number of subversive angles from which a renegade cell can operate - it is a wonder that cancer does not erupt more often in our long lives!

1 comment:

  1. Normal cell growth ( or quiescence) is triggered by various protein messengers, receptors ( antennae) and signal-processing ‘circuitry’. Many of the details of this cellular signaling circuitry have been pieced together by bio-researchers and oncologists over the last ten years. The plan of this circuitry provides the key to understanding the cell growth deregulation that creates human cancer. It also allows us to relate growth deregulation to the actions of specific genes. We have moved from a position of substantial ignorance to deep insight. The foundations of an effective program for the prevention and cure for cancer have been well laid.