Intratumoral heterogeneity: Clonal cooperation in epithelial-to-mesenchymal transition and metastasis

Neelakantan, Deepika; Drasin, David; Ford, Heide L.

doi:10.4161/19336918.2014.972761

Cited by 57 publications

(64 citation statements)

References 122 publications

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“…Consequently, several studies have started to focus on the ecological cooperation or competitive interactions between tumor populations (Merlo et al 2006;Moreno 2008;Neelakantan et al 2015;Tabassum and Polyak 2015). In primary breast tumors, recent research using mouse models has characterized the polyclonal origin of certain tumor types and the interclonal cooperation between multiple subclones (Cleary et al 2014).…”

Section: Clonal Cooperationmentioning

confidence: 99%

“…In the metastatic context, this phenomenon was first reported by coinjecting nonmetastatic cells with metastatic cells to increase the metastasis of the former (Miller 1983). Cooperation can be promoted by endocrine and exosome signaling between different clones (Martorana et al 1998;Neelakantan et al 2015). ECM proteins, such as SPARC, also serve as messengers of cooperation to enhance invasion and metastasis ( Fig.…”

Section: Clonal Cooperationmentioning

confidence: 99%

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Distinctive properties of metastasis-initiating cells

2016

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Primary tumors are known to constantly shed a large number of cancer cells into systemic dissemination, yet only a tiny fraction of these cells is capable of forming overt metastases. The tremendous rate of attrition during the process of metastasis implicates the existence of a rare and unique population of metastasis-initiating cells (MICs). MICs possess advantageous traits that may originate in the primary tumor but continue to evolve during dissemination and colonization, including cellular plasticity, metabolic reprogramming, the ability to enter and exit dormancy, resistance to apoptosis, immune evasion, and co-option of other tumor and stromal cells. Better understanding of the molecular and cellular hallmarks of MICs will facilitate the development and deployment of novel therapeutic strategies.

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Section: Clonal Cooperationmentioning

confidence: 99%

Section: Clonal Cooperationmentioning

confidence: 99%

Distinctive properties of metastasis-initiating cells

2016

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“…ITH is also explained by clonal (monoclonal or polyclonal) evolution resulting in genetic heterogeneity, by selective pressure induced by the microenvironment or by chemotherapy favouring one or more than one clone of cells, by the EMT theories and by inter-clonal cooperation mechanisms [61,[67][68][69]. Inter-clonal cooperation is also important for metastases, as clones favour metastases by sequential or simultaneous cooperation in motility, matrix degradation, vascular invasion or distant colonization [67,[70][71][72][73][74].…”

Section: Molecular and Genetic Heterogeneitymentioning

confidence: 99%

“…Inter-clonal cooperation is also important for metastases, as clones favour metastases by sequential or simultaneous cooperation in motility, matrix degradation, vascular invasion or distant colonization [67,[70][71][72][73][74].…”

Section: Molecular and Genetic Heterogeneitymentioning

confidence: 99%

Heterogeneity in Lung Cancer

2018

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Lung cancer diagnosis is a challenge since it is also one of the most frequently diagnosed cancers. Diagnostic challenges are deeply related to the development of personalized therapy and molecular and precise histological characterizations of lung cancer. When addressing these features, it is very important to acknowledge the issue of tumour heterogeneity, as it imposes several questions. First of all, lung cancer is a very heterogeneous disease, at a cellular and histological level. Cellular and histological heterogeneity are addressed with emphasis on the diagnosis, pre-neoplastic lesions, and cell origin, trying to contribute to a better knowledge of carcinogenesis. Molecular intra-tumour and inter-tumour heterogeneity are also addressed as temporal heterogeneity. Lung cancer heterogeneity has implications in pathogenesis understanding, diagnosis, selection of tissue for molecular diagnosis, as well as therapeutic decision. The understanding of tumour heterogeneity is crucial and we must be aware of the implications and future developments regarding this field.

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“…Within this vast literature, there is a growing appreciation for how the molecular and biophysical mechanisms promoting metastasis can be understood in an ecological setting. In a number of model systems, interactions between subclones, which separately do not exhibit metastatic potential, can induce EMT and metastases when introduced together to the same animal 20,21 . These observations indicate a kind of “division of labor” involved in development of metastasis, with some cells destabilizing extracellular matrix, others recruiting blood vessels, and others taking advantage of these conditions by detaching from the tumor mass and entering the circulation 18 .…”

Section: Adaptive Radiation and Ecological Niches: Understanding Tmentioning

confidence: 99%

Evolutionary scalpels for dissecting tumor ecosystems

Rosenbloom

Cámara

Chu

et al. 2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Amidst the growing literature on cancer genomics and intratumor heterogeneity, essential principles in evolutionary biology recur time and time again. Here we use these principles to guide the reader through major advances in cancer research, highlighting issues of “hit hard, hit early” treatment strategies, drug resistance, and metastasis. We distinguish between two frameworks for understanding heterogeneous tumors, both of which can inform treatment strategies: (1) The tumor as diverse ecosystem, a Darwinian population of sometimes-competing, sometimes-cooperating cells; (2) The tumor as tightly integrated, self-regulating organ, which may hijack developmental signals to restore functional heterogeneity after treatment. While the first framework dominates literature on cancer evolution, the second framework enjoys support as well. Throughout this review, we illustrate how mathematical models inform understanding of tumor progression and treatment outcomes. Connecting models to genomic data faces computational and technical hurdles, but high-throughput single-cell technologies show promise to clear these hurdles.

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Intratumoral heterogeneity: Clonal cooperation in epithelial-to-mesenchymal transition and metastasis

Cited by 57 publications

References 122 publications

Distinctive properties of metastasis-initiating cells

Distinctive properties of metastasis-initiating cells

Heterogeneity in Lung Cancer

Evolutionary scalpels for dissecting tumor ecosystems

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