Tumour cells coerce host tissue to cancer spread - PubMed (original) (raw)

Tumour cells coerce host tissue to cancer spread

Ilaria Malanchi. Bonekey Rep. 2013.

Abstract

A solid tumour is a complex structure and understanding this complexity is required to study the disease progression. Indeed, 90% of cancer deaths are due to metastatic spreading. Two aspects contribute to tumour complexity. One is the synergistic relationship between tumour cells and their associated host tissue, which persistently characterize tumour growth from the onset to metastasis. Another aspect is the heterogeneity of the cancer cells. It is now clear that within a tumour mass there is a hierarchical organization, stemming from a small amount of cells retaining the highest tumorigenic potential, named cancer stem cells (CSCs). Despite being one of the main studied topics in cancer research, CSC definition is still the subject of debate. Functional testing allows their identification, which is the ability of recapitulating the original tumour structure when transplanted in mice, but occasionally generates conflicting results. This has shaped the hypothesis that their key initiation ability is conditioned by their local microenvironment called niche. The CSC identity appears to be a contextual status where the ability to create a favourable supporting microenvironment may become a key hallmark of their tumour initiation capability. Remarkably, as shown in experimental models, the tumour-initiating potential of CSCs is maintained during metastatic progression, when disseminated cancer cells require the creation of their permissive niche to be able to trigger metastatic growth. This review will discuss the most recent findings on metastatic niche establishment and the cooperation between cancer cells and their newly recruited tumour-associated stroma forming the basis of metastatic development.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1

Figure 1

(a) Cancer stem cells (CSCs) definition. The cancer cell compartment of a tumour is constituted by a heterogenetic hierarchically organized mass of tumour cells. CSCs are the most tumorigenic pool of cells among the hierarchy defined using experimental assays. The size of the identified pool directly correlates with the challenge of the test applied; so, the higher the challenge, the smaller the amount of cells able to succeed. In vivo CSCs are defined for their ability to recapitulate the original tumour structure when transplanted in recipient mice. (b) The CSC hallmarks. (i) The first hallmark is the ability to induce microenvironmental changes in order to create their favourable environment, allowing the expression of their characteristic CSC capability. (ii) The ability to self-renew: to propagate while maintaining their CSC characteristics, as well as generating the other less potent cancer cells that constitute the original tumour cell mass. These first two abilities are linked to the in vivo tumour-initiation capacity of CSCs. (iii) The ability to maintain the tumour mass homoeostasis while the tumour grows and progresses. (iv) The intrinsic ability to survive chemotherapy or radiotherapy, and therefore the potential to generate relapses starting a new process of self-renewal and growth (iv–ii). From a certain moment of tumour progression, cells will start to disseminate within the organism and a new cycle of tumour initiation will require the same hallmarks at the distant site to enable metastatic outgrowth (iii–i).

Figure 2

Figure 2

Schematic representation of a breast cancer undergoing a metastatic progression to the lung. The diagram represents the evolution from the normal tissues (a) to the various phases of tumour and metastatic disease progression (b–g). (b) Once a tumour is established within a tissue, cancer cells start growing embedded within their tumour niche constituted by various reactive stromal cells and extracellular matrix (ECM) components. As the tumour progresses, cancer cells are released in the blood stream (c), where in the short period of time in the circulation (d) the disseminated CSCs can also find support on interacting with blood components such as platelets. (e) The process of metastatic dissemination at the secondary site may be helped by the presence of the pre-metastatic niche induced by paracrine signals from the tumour. The crucial event in the success of the process is the establishment of a metastatic niche (f) providing CSCs at the distant site with the favourable extrinsic signals normally produced by the tumorigenic niche at the primary site. At the target site, the choice between metastasis and dormancy will be made by some CSCs according to the successful establishment of this metastatic niche. However, if extrinsic signals allow quiescent niche formation (g), CSCs may persist in the infiltrated organ as dormant cells. Importantly, the dormant niche can potentially be reactivated to become a metastatic niche, where metastatic progression will occur.

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