The complexity of the metastatic cascade has led to the development of a plethora of 2‑ and 3‑dimensional in vitro assays to model the various steps of metastasis under a more controlled environment. These assays have been invaluable in cancer research not only as tools to delineate the molecular events that underpin metastasis but also to enable drug screens and validation of therapeutic targets. Here we review the advantages and limitations of current in vitro platforms used to investigate metastasis. In light of the overwhelming evidence showing that 3‑dimentional culture systems better mimic the tumor microenvironment and therapeutic response in vivo, recent advances made toward the development of 3‑dimensional culture systems and their applications are discussed in more detail. Relevant information on protocols and resources available to support scientists with an interest in metastasis research is also provided.
Bone is the preferred target of neoplasms such as prostate, breast, lung and melanoma cancers. Disseminated tumor cells (DTCs) from these cancers take advantage of the protective bone marrow niche normally occupied by hematopoietic stem cells (HSCs) and home to this space in a multistep...
Breast cancer frequently metastasizes to the skeleton where it usually causes bone degradation. The current therapies are directed to inhibition of osteoclasts, the bone resorbing cells. However, osteoblasts also play a role in bone loss and in sustaining tumor growth. Osteoblasts in the...
Cancer stem cells (CSCs) are defined as cells with self‑renewal ability, tumor‑initiating capacity, and the ability to give rise to more differentiated progeny. Though the frequency of these cells may vary among various kinds of tumors, they often represent a minor subset of tumor cells...
MicroRNAs (miRNAs) are small non‑coding RNA molecules that post‑transcriptionally regulate gene expression. They are linked to many developmental and pathological states including wound healing, cancer invasion, and metastasis, the primary cause of cancer‑related death. Colorectal cancer...
Recent experimental and epidemiologic evidence suggests that systemic physiologic stress‑responsive pathways may help shape the tumor microenvironment to promote metastasis. These pathways act through the peripheral sympathetic nervous system to release catecholaminergic neurotransmitters...
Improvement in modern primary cancer therapy ironically has led to an increased incidence of brain metastasis. Despite its clinical importance, mechanisms underlying brain metastasis are still unclear. As the brain lacks lymphatics, hematogenous dissemination is the most common pathway for...
The concept of organotropism is by no means novel; for over a century it has been observed that certain primary tumor types have a tendency to metastasize to specific secondary sites. Yet it is only since the dawn of the 21st century that genomics has emerged as a valuable tool for probing the...
Colorectal adenocarcinoma remains the best studied model of gastrointestinal cancer metastases in which in the clinical arena patients may achieve satisfactory long‑term disease free outcomes with a multimodality approach. Predilection for both liver and peritoneal metastasis development is...
Cancer metastases arise from a unique subpopulation of cancer cells that adapt to circumvent normal homeostatic mechanisms of cellular control. They are able to spread, invade, and thrive in non‑native environments. The clinical relevance of metastases is based not only on their lethality,...
Metastasis is the leading reason for the resultant mortality of patients with cancer. The past few decades have witnessed remarkable progress in understanding the molecular and cellular basis of this lethal process in cancer. The current article summarizes some of the key progress in this area...
With the advent of high throughput transcriptomics came the realization that large swathes of the un‑annotated genome variously referred to as “junk DNA”, “selfish DNA” or “gene deserts,” produce vast numbers of transcripts with low or no protein‑coding potential, that have...
Lung cancer is the leading cause of cancer‑related death in the United States and worldwide. The majority of patients present with metastatic disease. The overall prognosis is poor for these patients, with less than 5% surviving more than 5 y. A better understanding of the molecular biology...
Surgical resection is considered the definitive treatment for patients with solid neoplastic tumors. Recent experimental evidence, however, suggests that undergoing surgery may actually play a role—via activation of the surgical stress response—in promoting postoperative metastases....
Genitourinary malignancies represent heterogeneous group of diseases linked by anatomical and physiological function but different in almost every aspect of pathophysiology, molecular biology, prognosis and treatment of metastatic disease. Prostate cancer is by far the most common of...
The complexity of the metastatic cascade has led to the development of a plethora of 2‑ and 3‑dimensional in vitro assays to model the various steps of metastasis under a more controlled environment. These assays have been invaluable in cancer research not only as tools to delineate the...
Most cancer‑related deaths are due to metastatic disease, primarily reflecting the paucity of effective treatments once cancer has spread beyond the primary organ. Investigations into the molecular and cellular processes underlying the metastatic cascade are vital for streamlining...
The majority of brain tumors are not of primary origin from the cells comprising the brain’s physiologic milieu (such as glioma), but result from the spread of cancers outside the brain such as lung and breast. The dissemination of neoplastic cells from primary tumors and their effective...
Metastatic breast cancer, also known as advanced or stage IV breast cancer, is the stage in breast cancer progression where malignant cells from the primary tumor successfully create new tumors in distant organs. Patients diagnosed with advanced breast cancer, especially at a young age, have a...